Kyle tries to visit his cousin Shawn at The 4400 Center but is thrown out. Richard and Lily are desperate to protect their infant daughter, Isabelle from Collier and other maniacs, and a schizophrenic 4400 wants a huge communicative device and makes it a hospital's project from a minor position.
A baseball player is overwhelmed by a special 4400 ability. Collier is involved with a weapons' dealer. To Maia's delight Diana's sister visits them. Richard and Lily seek shelter at a motel where Isabelle takes some surprising initiatives.
A salesman's saliva has an extremely slimming effect on people. Lily suspects a new pregnancy as Richard stumbles onto a case of jealousy. So does Collier, and Shawn is disgusted by his moral. Kyle is tempted to join a wild students' party. Maia finds her aunt's work very interesting.
Some schoolchildren get startling abilities and some parents suspect child abuse by a 4400 who is their teacher. Jordan Collier changes attitude, especially towards Isabelle and her parents. Shawn is fascinated by a young homeless girl.
Tom Baldwin wakes up in a parallel or alternate world where he has married a woman two years ago but he has never seen her before. There is no trace of any 4400s from the future with special skills, and Jordan Collier is Governor.
After living for 8 years in an alternate world that only Tom and Alana remember the world with the 4400 has returned as it was at the second the 8 years started. A 30 year old 4400 woman wakes up and finds everybody else in her local community dead. Maia puts April's love for her to a test.
A male 4400 originally from Rwanda repairs bad chromosomes of unborn. Kyle is utterly despaired as he suddenly remembers what he did during his blackout. Richard attends a co-veteran's funeral. Diana makes a hard family decision.
On John Colliers'ø birthday NTAC receives threatening e-mails and gets attacked by terror. Kyle is concerned that an innocent will be convicted for killing Collier. Maia gets a mysterious infection and is treated at NTAC. Isabelle has broken off her special communication with her mother and transfers it to her father. At school a girl is very interested in Kyle.
7 of the 4400 have died and Maia gets worse all the time Out of suspicion and despair Diana threatens Dr. Hudson with a gun. Lily has run away with Isabelle and Richard pleads her to come back. Marsdem seems unable to avoid a long prison term which makes Alison contact Kyle.
In a broadcast, the Nova Group promises the world a demonstration of their power on October 19. Tom and Diana apprehend Gary, but he refuses to give any information about October 19. Meanwhile, it's learned that Shawn has been funding the Nova Group for months, unaware of their murderous intent. Meanwhile, Shawn helps Isabelle deal with the guilt of her mother's impending death. Lily dies peacefully.
Daniel Armand of The Nova Group launches an attack against Shawn causing mental illness. Isabelle seeks retribution. Alana tracks down a drunk driver responsible for the death of her husband and child.
Dr. Burkhoff continues his experiments on himself and forces them on another person and Maia has a nightmare where Diana looks like a monster. A rock star tries to involve Shawn in his health that demands almost all of his time.
Just as he's about to be wedded to Isabelle Shawn has seen Jordan Collier very alive and helps NTAC to search for him. April presents her new boyfriend to Diana, but soon after Maia tells Diana about a family enlargement.
A high school kid named Graham develops an ability which makes people worship him to the point of sacrificing their lives for him. Tom visits Isabelle in jail, hoping to get information on the whereabouts of Alana who's been missing for months. Marco calls Diana to let her know that her sister April has promicin and is nowhere to be found. NTAC gets a new director. Kyle meets a young woman named Cassie who has some advice about how to get Shawn out of his coma. Jordan shows up to deal with the high school kid.
Diana returns from Spain. NTAC tries to identify the person whose ability makes people's worst fears come true. Shawn returns home from the hospital and his brother Danny tells him that he's thinking about taking promicin. Kyle finds out some interesting facts about Cassie.
After taking promicin, an old lady named Audrey Parker develops the ability to astral project from her body. When she's murdered, her spirit tries to reach Tom and Diana to help them find her killer. Shawn decides to re-open the 4400 center and start healing again despite the government's warnings. Ben and Maia come to Seattle to visit Diana. Cassie leads Kyle to some interesting information.
Diana catches her sister April, who has survived a promicine shot and gained an ability the full potential of which she fails to grasp - to make anyone answer truthfully to any question posed by her. She has teamed up with a man she loves and they are blackmailing people who have dirty secrets. But then they bite more than they can chew and April's beloved gets murdered. The only way to get the people responsible to answer for their crimes would be for April to turn herself into NTAC custody and lose her precious freedom... Meanwhile, Shawn decides to run for the mayor's office and Isabelle helps Kyle translate the coded section of the White Light book - which results in a shocking revelation.
Now that he knows Kyle is Promicin Positive ("P+"), Tom sets out to track him down. His journey leads him to a town that is no longer on the map and the people of which are not ordinary. Meanwhile, Maia has terrible visions of 4400s and P+es being dragged to prison camps. And her visions always come true.
The NTAC nerd squad bring to their Director's attention a 4400, Curtis Peck, who was a shoestring budget film maker and continues to be one, except that his 4400 ability seems to be to receive script pieces that combine to tell the true, complete answers to haunting questions, like "What happened to Jimmy Hoffa?" and "Who shot JFK?". And now he's missing and he left a video message where he told that Jordan Collier is not the real threat - there is something far more dangerous, and now they are after him. Peck's producer shows a trailer of the film Peck was supposed to start making, "The Marked", to Tom and Diana, and it paints a new, frightful picture: In the future the 4400 are supposed to prevent, exists a group of powerful individuals who like their time just the way it is and have irrevocably replaced the minds of ten important persons of the present time with the minds of their agents. Peck calls them "The Marked" because each one supposedly has an X-shaped mark behind their left ear because of the mind-replacing procedure. So far, Peck has received only one name. When Tom and Diana start investigating, Peck's unbelievable conspiracy theory starts to gain credibility... Meanwhile, Shawn meets Collier and tells him that he can't join Collier's cause because he needs to focus on his politic opponent, Gabriel Hewitt. Soon after that, Hewitt suffers a stroke. A coincidence?
Shawn gets bad publicity when he ends up having sex with the daughter of a woman whom he cured and it turns out to be a trap when the girl tells the media her story. Maia paints a vision that at first doesn't make sense, but then the nerds at NTAC match it to the most polluted - and more crucially, abandoned - part of Seattle, making it the perfect hiding place for Collier, his 4400s and P+es. Tom and Diana try to investigate, but find out that Collier has set an uncrossable perimeter around his "Promise City". When Collier starts broadcasting live footage of a P+ turning the poisoned water perfectly clean and declares his peaceful intentions but also states that they are not to be interfered, the government sends in a squad of super soldiers to take him down.