- "The Agency" has put Lian and Gabe on trial for crimes they did not commit while they secretly plot to distribute Syphon Filter, a deadly virus, throughout the population. And with Gabe and Lian on trial there would be no one to stop them.
- Taking place after Syphon Filter 2 (2000), Lian Xing is finally cured of the virus. However, Teresa Lipan got killed by Chance, making Gabriel Logan kill him. During the funeral, Gabe, Lian, and Lawrence Mujari are still trying to eliminate the Syphon Filter threat that is still going on. After killing a rebel Chinese general Shi Hao in Tokyo, Gabe and Lian escape. Lawrence manages to call the Senate and testify for themselves. The player controls the characters' past missions including the mission to Costa Rica. While one character testifies, the others are trying to save the world from the virus. Will Gabe and Lian manage to clear their names and save the world, or will they still remain fugitives? Only the player can find out.—Zero 88
- Gabe, Mujari, and Lian are mourning Teresa Lipan in Whispering Woods. Hadden is then seen talking to Aramov, who complains that with administration pulls, he could end it. Hadden responds by saying he has other plans for Gabe Logan, that hearings have been scheduled and that he has to blame a party.
At the Senate house in Washington D.C., Mujari and Lian are standing outside in a hallway while Gabe is inside talking to Hadden. Hadden tells Gabe his own version of the Syphon Filter Virus situation, saying that "There is no conspiracy, no arms consortium, only a traitor. Acting alone, or with his friends". He then asks Gabe if he has ever assassinated a world leader. Gabe says no, but remembers a mission in Tokyo in which he shot Shi Hao from across the street in a hotel.
In the first flashback, Gabe is dropped off at a hotel, where Lian tells him that he has to go to room 413. Gabe goes up to the desk and asks for the key. He then goes to the elevator. After a talk with the elevator attendant about the weather, Gabe goes to the room. He receives a transmission from Lian to get his equipment from the bathtub.
Gabe gets his equipment and goes to the window. He draws a bead on Shi Hao, who is currently in a meeting/interrogation with the JRA. Gabe watches as they are beating a man. He takes the shot, only after eliminating the rooftop sniper, and kills Shi Hao. Shi Hao's highest ranking lieutenants and other men in the building rush to attack Gabe, but he takes them out easily.
JRA members have entered the hotel and have captured the daughter of a Japanese official hostage. Gabe eliminates most if not all of the grunts and, in the process, gets an explosive round shotgun from the man who took the beating across the street (if said man was not killed). He rescues the daughter of the Japanese official. Gabe leaves the hotel and Lian tells him that hearings have been scheduled.
The second mission is also a flashback. In it, Gabe details the events leading up to the D.C. incident in 1999. Gabe and Lian were sent to Central America in Costa Rica to meet with Ellis, who was undercover, infiltrating the ranks of Rhoemer's terrorist group.
Gabe and Lian were airdropped into the area, but were separated with two soldiers in between them. After they meet up, they notice multiple automated turret emplacements. Gabe and Lian are only able to take out the guns with grenades, and at the second emplacement, Lian runs out, forcing Gabe to destroy the rest on his own.
Rhoemer has Anton Girdeaux set fire to all the plants in the area, and has Aramov kill Ellis. Gabe and Lian show up right after Ellis was killed. Gabe and Lian are told by Edward Benton to continue Ellis' mission. Gabe must secure 3 samples of the plants, and destroy Rhoemer's assault chopper; Lian must find out what they were growing.
Gabe gets his samples, takes out the chopper, rescues two slaves and finally comes across a minefield. While he was collecting the samples, Lian tells him that Rhoemer was heading for a landing strip. Gabe crosses the minefield guarding said airstrip. Benton then calls and tells Gabe to meet up with Lian. He ignores the order and heads for Rhoemer. Gabe procures a jeep and trails Rhoemer to his C-5 Galaxy transport. The former manages to get on and find the exact same type of armor he would later find used by Jason Chance. Gabe finds Rhoemer donning the armor and shoots him with a USAS-12 to knock him out of the open cargo bay door. However, Rhoemer had a parachute on, and is able to escape.
The next testimony for Hadden to hear spans two missions, and it is Mujari who gives the account. Mujari explains the first time he came into contact with the Agency and the Syphon Filter virus. In 1984, Mujari was working with the ANC, in South Africa, to free repressed Africans. Mujari freed two slaves, saved his partner, Dejesus, destroyed the mines with explosives, spoke with Foreman Jones about the sick workers, and sent the transmission to HQ, which was normally Venik Smith's mission; he was killed by two soldiers when Mujari reached the Transmitter Tower. When a movie that shows him going down the elevator and looking at the sick workers, he tells Hadden in his testimony that he has "found [his] brothers, but [he] would not be setting them free."
We find that after the testimony that Mujari kept the South African samples, and Teresa Lipan, who was working in the WHO (World Health Organisation), came to his lab and saw the South African sample. Hadden says that Mujari gave the virus to Teresa, but Mujari said that he "thought nothing of it," and that Teresa asked him to work on the virus in a lab. Hadden asked if he remembered which lab Teresa took Mujari to. Mujari replied "Of course. It was Pharcom."
When it was Lian's turn to testify, she tells about the events that happened in Kabul, Afghanistan during 1987. At the time of the event, she was gathering evidence of Soviet troop movements led by Uri Gregorov while she was an MSS agent. She was ambushed at one point by the Soviets, and was saved by a U.S. Army Ranger. The Ranger that saved her was none other than Gabe Logan. Gabe debriefed Lian on his mission to deliver weapons to the local rebels in the area, and Lian agreed to create a distraction for him.
While Lian was testifying, Gabe was doing a joint operation with an MI:6 team headed by Margeret Powers. They tracked a shipment of the Syphon Filter Virus in Dublin, Ireland and had objectives to destroy the ship in order to prevent the virus from falling to the wrong hands. He planted three explosives in three different cargo holds, and one decoy explosive in the engine room. Gabe also recovers the shipping manifest to find out where the virus came from.
Lian then started telling about her side of the operation in Costa Rica saying that Rhoemer had kidnapped an impressive list of world-renowned scientists and medical technicals to work at his labs. Benton ordered Lian to get the scientists out alive in order to find out whatever the plants were used for. She was also ordered to collect the physical sample of the virus, collect data disks, and destroy the seven computers that were inside. During the mission, we discover that Elsa Weissinger was one of Rhoemer's lab technicians. She was ordered by Rhoemer's men to tell where her mentor, Dr. Fried, was so her life would be spared. It's discovered that the plants were part of creating the Syphon Filter virus.
At the time of testifying about the Costa Rica operation, Gabe and the MI:6 team were under attack by the Irish Republic Army. The IRA discovered the Agency consortium's plans to drop off viral containers at this particular dockyard and already unloaded several truckloads of the virus while the bombs were planted on the ship. Gabe and the MI:6 team set out to prevent the trucks from the leaving the area and find out who leaked the shipment to the IRA in the first place. After containing and destroying all but 1 truck, an MI:6 agent named Nigel Cummings was revealed to be pinned down with the final truck. After getting to Nigel and the truck, Nigel attempted to drive off with it, almost running over Gabe in the process and in turn, revealing Nigel as the double-agent of the IRA, so Gabe ran after and killed Nigel before he escaped with the last truck.
It was Gabe's turn to testify and he told about his mission to deliver the weapons to the rebels in Afghanistan during 1987. Gabe, Ellis, and Benton were the only survivors of a destroyed convoy. While Benton was driving the truck, Gabe and Ellis were repelling attacks from other Afghan rebel factions while clearing away all obstacles. Upon entering Kabul, Lian's diversion worked as the heavily guarded portion of their entrance was temporarily empty. Unfortunately, the rendezvous point had a Soviet T-64 tank guarding the town square. Gabe had to take out the tank using C-4 charges. Gabe then reveals to Hadden that Benton's contact was not an Afghan rebel but a Soviet agent. It turned out that Benton did not work for the CIA. He worked for the Agency which was supplying weapons to the Soviets. However, Benton shot the Soviet agent dead before ordering Ellis and Gabe to leave the weapons for the rebels. He recruited Gabe and Ellis into the Agency several years later.
While Gabe was testifying, Lian was working in the Tanami desert at Australia with tactical support provided by Maggie. The manifest recovered by Gabe led her to the desert and also found out that Dr. Elsa Weissenger was running the medical end of the operation. Lian intends to capture Elsa, take photographic evidence of genocide, sabotage the compound's communications systems, take out as many terrorists as possible, and save the local aborigines from being used as test subjects. Upon finding Elsa, Lian forces her to synthesise the vaccine after getting three compounds to make it. Before going off to save the villagers, Elsa gives Lian a data disk containing information about Mara Aramov and the agency she had made as an insurance policy in case Aramov double-crossed her. Lian saves the villagers and kills Commander Silvers in the process, although when Lian returns to the chopper, Elsa is missing.
Hadden starts to accuse Gabe of lying in his deposition and is about to have him arrested as a traitor and for killing many people (including Jason Chance and Teresa Lipan), but Teresa herself barges in, arguing that Gabe is innocent because she faked her death. Hadden was shocked at her appearance. Teresa makes a testimony of what happened when she was an ATF agent in Western Montana, Paradise Ridge. She was sent in to find missing ATF agents investigating a satellite falling from orbit, when she ended up helping two FBI agents saying that they needed back-up in order to take down a militia sniper. Teresa provided back-up for the agents, but she ended up being in a middle of a conspiracy.
It turned out that a militia survivalist named Earl Oakton was captured by the Agents and was executed in cold blood. The acclaimed FBI agents were corrupt NSA agents who were hell-bent on killing the Oakton family to cover up the illegal data they had taken from the satellite. One NSA agent captured Teresa after she watched Earl Oakton get executed. Teresa's captor killed the executors and it was revealed that Gabe Logan (in disguise) was the one responsible for saving her life. Gabe is concerned about retrieving the data. Teresa does her best to save the militia men and her fellow ATF agents from the NSA hitmen. She eventually meets up with the Oakton family, recovers the satellite data, and extracts them from the area with Gabe.
At the end of the testimony, it turned out that Teresa was shadowing Hadden the entire time and found out that he has been talking to Mara Aramov. Gabe appears with federal agents with a warrant to arrest Hadden. Before any action could be taken, Aramov interrupts and shoots all in sight, but Gabe and Teresa escape danger. While Teresa monitors the wounded agents, Gabe attempts to pursue Aramov while saving captured federal agents and finding the code to disarm the bombs she had planted around the senate building. After sending the codes to Mujari, Gabe continues his pursuit, eventually entering a subway train and shooting Aramov.
Upon Aramov's capture, Gabe is now given the head position of the Agency, which was eventually labelled the IPCA. Before any protagonist could have a break, Mara Aramov escaped the hospital. Gabe however was more concerned about forming the IPCA and decided to settle this unfinished business with Mara at a later time. The ending clip shows Mara, in a mini-sub, recovering some of the shipment of the Syphon Filter virus from the S.S. Lorelei's wreckage.
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