In April 2002, more than two decades after a massive international effort that was meant to have rid the world of smallpox forever, the dreaded killer disease returns with a vengeance. An unknown terrorist, who somehow obtained a sample traceable to the former Soviet bioweapons program, deliberately infects himself and walks around New York City. Within days, unwitting travellers flying out of New York airports spread the disease around the world. The pseudo-documentary shifts back and forth between interviews with medical and law enforcement personnel recounting their desperate attempts to contain and combat the plague and with survivors telling of the triple nightmare of coping with the plague itself, the collapse of society around them and the draconian measures of the authorities in dealing with both.