A 4400 terrorist marks the dead Jordan Collier's birthday by planting a device within NTAC that causes all the males to turn savage, forcing a lockdown of the facility. Meanwhile, Lily suspects the 4400 Center has devious plans for Isabelle; Shawn adjusts to being a media figure; and Kyle kindles a romance.

In Nina's absence, Dennis Ryland oversees Tom and Diana's investigation of a deadly epidemic affecting the 4400. Meanwhile, Isabelle is examined without Lily's consent; Alana begins confusing reality with the fantasy she shared with Tom; and an ailing Shawn abdicates control of the 4400 Center.

Tom and Diana discover that the source of the disease that threatens the lives of the 4400 is linked to a conspiracy to inhibit their burgeoning abilities. Meanwhile, Lily experiences harrowing hallucinations; Richard organizes resistance to the quarantine; and Kyle decides to own up to the Collier shooting.