Jack pushes the envelope in an attempt to force Saunders to disclose the location of the missing vials. Sherry meets with David to discuss her terms, while Wayne breaks into her home to find the incriminating evidence. Tony finds himself facing a harsh penalty because of his efforts to save Michelle.
Jack attempts to use Saunders' daughter as leverage to gain control of the virus, while Palmer must deal with the discontented press. Michelle gets the results of her test, while Adam finds that the virus has struck too close to home. Tony finds himself compromised when Saunders exploits his only weakness.
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 learns of a woman who can lead him to Saunders, but a surprise attack shifts the balance of power. As Gael's symptoms get worse, Michelle devises a way to relieve the suffering of the victims at the hotel.
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. Amador and Alvers meet with the man who is planning to unleash the virus in LA within the hour. Michelle and Gael locate the target area, but things really hit the fan when they attempt to capture Alvers in the process of releasing the virus. Wayne argues with Sherry over the consequences of Milliken's death as the police turn up the heat on Julia.
Jack and Chase interrogate Nina, but the worm turns when she causes havoc with the CTU computer systems. Chappelle puts Chloe under guard when she refuses to answer questions about the baby, but is forced to release her when she is the only one who can deal with the crisis. Sherry takes her battle directly to Alan, forcing Julia to act as her accomplice.
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. Kim becomes suspicious of Chloe when her story about her baby doesn't check out. Sherry finds a witness who can damage Milliken, but her advantage is short-lived.
Claudia manages to free Chase from his captors, but she pays a high price for her efforts. Wayne turns to Julia, while Palmer calls on Sherry for help against Milliken. Jack and Ramon make plans to get to Nina, in the hopes of intercepting the virus. Chloe's work at CTU is disrupted when she is forced to take care of her baby.
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. Kim and Michelle worry about Tony's mental ability when he continues to make mistakes. Jack and the Salazars meet with Amador, but the deal turns sour when Nina Myers appears on the scene and competes for the virus.
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. Jack has a private moment with Claudia and she blasts him for leaving her behind when he arrested Ramon. Chase arrives in Mexico, but is captured by Hector's men. Ramon devises a way for Jack to prove his loyalty to them. Anne manages to clear Palmer's name, but she breaks off her relationship with him.
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. Gael is captured while trying to escape from CTU. Chappelle interrogates Gael but is interrupted by Tony, who claims that Gael is part of a bigger plan. Anne is given a chance to clear Palmer's name, while Chase heads for Mexico to rescue Jack.
Jack's efforts to break Ramon out of prison go awry when they are captured by a group of inmates during the riot. Chloe unwittingly stumbles on to Jack's drug problem and she is forced to reveal his secret to Kim and Michelle. Palmer begins his debate with Keeler, while Kyle prepares to sacrifice himself to save Linda.
Michelle is torn by personal and professional obligations when she must take charge of CTU after Tony is wounded. Kyle and Linda are captured by Hector's men. Jack and Palmer have a secret conversation, leading Jack to take drastic action in the face of the Salazars' threat. But Jack's plans are complicated when Chase gets in the way. Anne pushes Palmer back onto moral ground in the face of her ex-husband's blackmail scheme.
Jack and Hector both search for Kyle, while Chase finds himself out of action at CTU. Wayne and Palmer argue over the implications of Anne's past, while Ramon takes out one of his opponents in a surprise move. Tony leads an operation to get Kyle, but tragedy strikes when Salazar's man gets there first.
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. Linda breaks up with Kyle when she learns that he is planning to make a drug delivery. Wayne approaches Palmer with information about his girlfriend that could damage his chances for re-election, while a CTU employee is not what he seems.
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 his new partner, Chase Edmunds, prepare to sign a deal with Salazar at the prison. Salazar delivers a mysterious warning to Jack before killing his lawyer. Palmer is alive and well, and has returned to LA for the first time since the attack three years ago. He is running for re-election and is preparing for an important debate with a rival senator. He is accompanied by his brother, who happens to be his chief of staff and his doctor, who also happens to be his girlfriend. A young boy, Kyle Singer, is seen examining a large, mysterious bag of white powder. He plans to deliver it to some dealers later that day, but he is being watched by Salazar's men. Kim now works at CTU and has been dating Chase for three months. Kim wants to tell her father, but Jack has a mysterious health problem that may make things more complicated.