The filming of the alley scene was very troublesome for the filmmakers, due to the rough neighborhood. The alley was littered with garbage, most of which was used in the film, and plagued with large rats. Local residents angered by the noise created by the film crew would throw bottles and paper bags filled with feces from windows at the crew in the alley below. Worst of all, the film crew found a dead body hidden among the garbage. "The most horrible places I've ever had to film in were the alleys in downtown Los Angeles," Shane Mahan commented, "and Predator 2 was shot in a lot of those disgusting alleys. They were dirty and depressing and gross, with people peeing on walls. We'd be rigging something, and there would be rats there."
After being offered the lead, Danny Glover was quick to jump aboard the movie, as he knew of few movies that had "a black man fighting a supernatural being". Director Stephen Hopkins said that the studio's only concern was that an Afro-American leading man would limit the film's profitability in some countries (e.g. South Africa), but they eventually agreed, given Glover's popularity from the Lethal Weapon movies. Hopkins also stated that Glover's presence worked as a magnet on several other actors, who were keen to work with him. Several of the hunting party members were played by players from the Los Angeles Lakers; Glover was a big fan, and when the production needed several very tall people to play the background Predators, he asked them to help out.
Stephen Hopkins was given the task of directing Predator 2 (1990) after greatly impressing the studio when directing A Nightmare on Elm Street: The Dream Child (1989). He had been given just four weeks to shoot, and a further four weeks to edit the film, while also overseeing special effects work. This meant that he had to shoot on one stage while the crew dressed the other, allowing them to shoot almost continually. Hopkins said that he managed because he was 28 at the time, and required little sleep.
The Jamaican voodoo posse gangs seen in the film were based on actual gangs that were terrorizing New York City and Kansas City in the mid to late 1980s. The Jamaicans were not played by actors or stunt people, but real-life bouncers, because as director Stephen Hopkins said, they had to be able to be physically intimidating and die "fantastically horribly".
The spear weapon that was used in the film disappeared and was reported stolen after filming was completed.