Three years have passed since the events of Day Two. A van deposits a dead body outside the LA Health Unit. The body is infected with a deadly virus. Tony, now in charge of CTU, learns that this is a blackmail tactic to get the US government to release a drug lord, Ramon Salazar, whom Jack has just brought down, before Salazar's brother releases the virus into LA.
Jack and Chase quarrel over Chase's relationship with Kim. Meanwhile, they learn of a lead to the possible whereabouts of the virus after raiding a crack-house.
Jack and Hector both search for Kyle, while Chase finds himself out of action at CTU.
Michelle is torn by personal and professional obligations when she must take charge of CTU after Tony is wounded.
Jack's efforts to break Ramon out of prison go awry when they are captured by a group of inmates during the riot.
Jack and Ramon struggle to evade the authorities, while Palmer must shut the debate down because of the prison break.
Ramon holds Jack hostage as he flies to Mexico. Ramon plans to kill Jack, but Jack manages to hold him at bay until the plane lands. Ramon then learns that Jack and Hector are working together to break him out of prison.
Palmer and Chappelle view a message from Jack, explaining his undercover work with the Salazars. Meanwhile, Hector tries to convince Ramon that they should deal with Bauer so that they can get their hands on the virus.
Palmer clears Anne's name with the press, but he finds that he is facing a new problem when his biggest campaign contributor reveals a startling secret about Wayne.
Claudia manages to free Chase from his captors, but she pays a high price for her efforts.
Jack forces Nina to work with him to get the virus from Amador.
Things finally come to an explosive head as Jack, Ramon, Nina and Chase all close in on the virus. But the deal takes an unexpected turn when Amador pulls a fast switch.
Jack and Chase interrogate Nina, but the worm turns when she causes havoc with the CTU computer systems.
Tony interrogates Nina about Alvers' location, while Chappelle orders Jack to undergo a medical examination in light of his drug use.
Chappelle threatens to pull Jack from the investigation for killing a material witness, but Jack persuades him to hold off when they find a fresh lead on Amador's whereabouts.
Jack and Chase track Amador in the hopes that he can lead them to the man behind the virus attack.
Saunders begins making demands on the President. He forces Palmer to hold a strange press conference and then orders the death of the CTU agent who can trace him.
Jack and Chase race against time to capture Saunders before the deadline, while Chappelle plans an escape.
Jack reluctantly works with Kim on an undercover job that may help them gain an advantage over Saunders.
Jack attempts to use Saunders' daughter as leverage to gain control of the virus, while Palmer must deal with the discontented press.
Tony works to free Jane from CTU before Saunders can harm Michelle, but Chloe and Jack become suspicious of his activities.
Jack and Tony clash as the time for the hostage exchange draws near.
Jack pushes the envelope in an attempt to force Saunders to disclose the location of the missing vials.
Jack and Chase must make a powerful sacrifice when dealing with the virus.