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When casting for the mutants, associate producer Cody Zwieg explained: "We needed to find actors who could not only perform the stunt work, handle the extensive makeup and perform in that makeup, but who truly could embody the fierce, primal nature of the mutants way of life." To play the part of Pluto, Aja looked to Michael Bailey Smith, who had been in a Nightmare on Elm Street 5: The Dream Child (1989). They cast Robert Joy as Lizard, as he appeared in films such as Amityville 3-D (1983) and Land of the Dead (2005). Ezra Buzzington, impressed with the filmmakers, agreed to play the role of Goggle and even watched a documentary about human cultures engaging in cannibalism. To play the mutant leader, Billy Drago was cast. Drago had a similar role in Brian De Palma's The Untouchables (1987) and other horror features. The most difficult mutant to cast was Ruby, who was a "touch of sweetness to the madness of the mutants." Laura Ortiz was ultimately cast, making her film debut.
The gas station set was built on location in Morocco. It was so authentic that occasionally someone not involved in the production would stop to buy gas.
The mutants were created by CGI, physical effects or both. Most of the mutants with full deformations were created by prosthetic makeup. But the deformed children who were playing were digitally distorted using tracking dots on their faces. Ruby was a mixture of the two, using the tracking dots for distortion and prosthetic teeth.
(at around 3 mins) The photos of mutations that play during the opening credits are not of atomic mutation, but birth defects caused by the use of Agent Orange in Vietnam.