In New York City, a deadly disease called Strickler’s disease, spread by cockroaches, is killing hundreds of children. Doctor Peter Mann (Jeremy Northam), deputy director of the CDC, recruits entomologist Doctor Susan Tyler (Mira Sorvino). She uses genetic engineering to create the Judas Breed, a termite/mantis hybrid that releases an enzyme to accelerate the roach metabolism such that they cannot get enough nourishment and die. The roaches die off and Peter and Susan marry happily.

Three years later, a priest is chased and dragged underground by a mysterious assailant. The only witness is a young autistic boy named Chuy Gavoila (Alexander Goodwin), who has the skill of imitating noises and refers to the attacker as Mister Funny Shoes. His guardian, a subway shoe-shiner named Manny (Giancarlo Giannini), does not believe his story. Two kids sell a weird bug to Doctor Tyler, who tests it and finds it very similar to the Judas Breed.

Looking for specimens, the kids go down to the subway tracks, find an egg sack, and are killed by the same weird assailant. Chuy, looking for Mister Funny Shoes, goes into the dead priest’s church and is abducted. Doctor Mann, his assistant Josh Maslow (Josh Brolin), and MTA officer Leonard Norton (Charles S, Dutton) enter the tunnels, but Peter and Leonard get stuck and send Josh for help.

Susan sees what seems to be a shadowy human figure in a trench coat on a train platform, but as she approaches, it spreads its wings and becomes an insect the size of a man. It grabs her and carries her into the tunnels. Josh is killed by something similar. Manny, searching for Chuy, rescues Susan, Peter, and Leonard, and they barricade themselves inside a subway car. Susan thinks the Judas Breed’s accelerated metabolism caused them to reproduce just as fast and evolve tens of thousands of generations in three years, growing in size, developing lungs, and learning to mimic their prey—human beings. While they plan to get the subway car moving again and escape, Susan speculates that the Judas Bug will spread through the tunnels and overwhelm the city unless they can kill the single fertile male.

Trying to switch the tracks, Manny finds Chuy, who has survived because of his ability to imitate the bugs’ clicking communication, but Manny is killed by the male. Susan looks for him and finds only Chuy. Leonard’s injured leg is bleeding and he creates a diversion, knowing that the scent will attract the bugs even more. He is killed. Peter finds a dumbwaiter and puts Susan and Chuy in it. As they escape, he blows up all the bugs with a leaking gas pipe, diving underwater to escape the blast. The Judas male escapes and goes after Chuy but is distracted by Susan, who lures it into the path of a train to its death. Susan and Chuy make it to the surface, thinking that Peter has died in the blast, but he is alive and well.

The film was directed by Guillermo del Toro, written by him and Matthew Robins, based on a short story by Donald A. Wollheim. It was filmed in Toronto, which often subs for New York. It is typically del Toro, with insects, clockwork, and monsters in dark places, found in brooding shots of dark, cluttered, dirty spaces, according to del Toro’s always meticulous plans. He fought tooth and nail with Bob Weinstein of Miramax, who thought it wasn’t scary enough. Weinstein lectured del Toro on how to make a movie and tried to get him fired, but Mira Sorvino defended del Toro and Weinstein let him finish the film, though he insisted on the final cut. Critics gave mixed reviews to the Weinstein cut, wishing that he had left del Toro alone. It was del Toro’s only bad experience making movies, but he got to do a director’s cut later for Blu-Ray.

Mira Sorvino, it seems, had just taken home an Oscar for Mighty Aphrodite and threatened to quit unless the Weinsteins backed off. She was supported by her boyfriend Quentin Tarantino. Harvey Weinstein, serial molester of women and potted plants, was so into scene-cutting that he was called Harvey Scissorhands. Del Toro had wanted Andre Braugher for Doctor Mann so the film would end with a white woman, a black man, and a Hispanic child, as del Toro’s vision of the future. The Weinsteins thought the public was not ready for this. Del Toro’s original idea was to have God, fed up with humans, replace them with giant cockroaches, but the studio wanted a scientific explanation and a happy ending.