A telepathic 4400 comes to NTAC seeking help with his ability, which is promised so long as he helps to investigate Collier's activities. Diana's sister, April, arrives for a surprise visit. Kyle finds that his tuition fees haven't been paid.
A 4400 whose ability is to produce an enzyme that causes weight loss puts it up for sale, with deadly consequences. Kyle starts blacking out. Jordan spends a lot of time with a celebrity who's at the Center, causing Devon to attempt suicide.
Tom and Diana are called to a possible child abuse case with a 4400 but find that she is bringing out latent talents with her ability. Shawn reaches out to help some homeless people whom he encountered. Richard and Lily are discovered by Collier, who offers a place at the Center and help with NTAC in exchange for a chance to talk to Isabelle.
Maia has a vision about Jordan Collier's death, prompting an all-out response by NTAC to stop it from happening. Shawn deals with the consequences of showing his healing ability to the homeless. Jordan consults Isabelle.
Tom and Diana are given a case of a 4400 woman who had survived the death of her entire town. It soon comes to light that she may be the carrier of what killed them. April starts using Maia's ability to win at gambling, causing Maia to distrust her. Shawn takes over the Center, getting help from Matthew Ross. Kyle remembers what he did during his blackouts.
Another 4400 healer is found, who is identified as a war criminal wanted by Rwanda. Shawn is advised to reach back out to his family. Richard goes to the funeral of his wing mate and confronts his abuser from just before he was abducted. Kyle is offered a place at the 4400 Center but disappears. A sketch of Collier's killer is distributed.
On Jordan Collier's birthday, NTAC is attacked by a 4400 ability. Kyle is attracted to a girl in his class. Lily becomes suspicious of the Center's treatment of her daughter. Shawn invites Kevin Burkhoff to the 4400 Center to continue his research. Maia becomes sick with a mysterious illness.
Around the world, 4400s start getting sick, prompting Dennis Ryland to return to Seattle NTAC and make a call for all 4400s to return to quarantine. As Tom and Diana continue their investigation, the possibility that NTAC caused the illness becomes evermore present. Kyle helps out the family of the man accused of killing Collier.