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A comet is due to pass by Earth, but its trajectory changes to a collision course, causing widespread panic. When the comet appears to slow down — as if it's coming in for a landing — 4,400 people are deposited in an explosion over Highland Beach.
The returnees — "the 4400" — have been missing from months to years. None have any memory of where they've been, none have aged, and a small number are beginning to manifest paranormal abilities. Tom Baldwin and Diana Skouris, two Homeland Security agents, are appointed to find out what happened to the 4400.
The 4400 are attacked by a series of bombings after Barbara Yates makes their names and addresses known to the public. Tom, Diana and Dennis try to put an end to the bombings, while at the same time Tom is coping with Kyle's erratic behaviour.
Warren Lytell, an agent from Washington is sent to "monitor" the team's progress on the 4400 investigations. Jordan Collier offers protection to members of the 4400, while Richard and Lily begin to question his motives.