Three years later; CTU receives a threat that Mexican drug lord Hector Salazar is planning on releasing a deadly contagious virus in LA unless Jack gets his brother Ramone Salazar out of prison. President Palmer prepares for a presidential debate with Senator John Keeler.
After Goss' infected body is dropped at the hospital Jack and Chase begin to trace his last known locations while CTU tries to figure out how the virus is gonna be unleashed to the public at large. Once they figure out it's gonna be spread through cocaine shipments CTU begins to track down drug dealers in East LA. President Palmer considers canceling the debate.
Tony and one of Salazar's cronies close in on a young drug trafficker who may be unknowingly carrying the virus. Jack informs Kyle Singer's parents that he may be infected. Wayne becomes concerned over David's latest affair when he learns the woman's ex-husband will perjure himself over sworn testimony he gave years earlier unless the President pays him not to.
In order to get Ramon out of prison Jack asks for President Palmer's permission to instigate a prison riot. Michelle takes over command of CTU after Tony is injured. Chase disobeys orders and fiercely interrogates Roman as Jack puts his plan into motion. President Palmer has Wayne call off the meeting with Anne's ex-husband. Drug dealer Kyle Singer is captured by Salazar's men.
Jack and Ramon are captured by dangerous prison inmates after trying to escape. President Palmer begins his debate with Senator Keeler. At CTU, Chloe O'Brian discovers evidence of Jack's heroin addiction.
Jack and Ramon try evade military helicopters when they make a run for a plane scheduled to leave for Mexico. Palmer cancels the debate. Kyle Singer learns that he is not infected with the virus. Kim discovers that Gael Ortega might be working with the Salazars.
Ramon holds Jack hostage as they fly down to Mexico. Regional Director Chappelle interrogates Gael; Tony returns prematurely to CTU to reveal Gael's true allegiance. Chase disobeys orders and heads for Mexico to rescue Jack.
A snag in the sale of the virus leads the Salazars to question Jack's motivations and as a result they put his allegiances to the test. Claudia works to help Chase escape after Jack informs her of his real priorities. Tony's ability to run CTU is called into question. Palmer is put into a difficult position regarding his brother.
In order to get closer to the virus, Jack tries to make Nina believe he still has feelings for her. Wayne tries to gain the trust of Julia Milliken when Alan Milliken starts making demands. Chase convinces Salazar's girlfriend to help him escape.
Jack and Nina prepare to meet with Amador, the man selling the virus; CTU organizes an ambush. Ramon and Hector have a falling out. President Palmer asks his ex wife Sherry to help with the Milliken situation.
Nina releases a deadly computer virus into CTU's systems after getting captured by Jack and Chase. Sherry runs out of options and decides to directly confront Alan Milliken but things go too far. Chloe and the rest of the tech crew work overtime to combat the virus.
Regional Director Chappelle forces Jack to undergo a medical evaluation for his heroin addiction. Tony interrogates Nina Meyers. Julia Milliken confronts Sherry after Alan dies while Wayne and President Palmer prepare for the fallout. Nina tries to escape custody after collapsing during the interrogation.
Amador and his people receive orders from their client to release the virus in the Chandler Plaza Hotel. Jack closes in on Amador but it's too late. Michelle and Gael alert the Chandler's Chief of Security to the dangers of the threat.
After the interrogation goes nowhere, Jack and Chase let Amador escape hoping he will lead them to his client's location. Michelle places the hotel under quarantine and must make a difficult decision in how to handle the ensuing panic. President Palmer is put into a awkward position when handling the Milliken situation.
President Palmer gives into Stephen Saunders's strange demand of placing an seemingly nondescript phrase into a speech in the hopes of delaying another viral outbreak. Michelle takes control of the situation inside the hotel. Jack and Chase bring a suspect to the local branch of MI-6 as Saunders launches an attack on the building.
Jack has to comply with another one of Saunders' demands: the death of Regional Director Ryan Chappelle. Michelle discovers that one of the infected hotel patrons got out before the quarantine was enforced.
When CTU learns that Saunders has a daughter attending an LA university they must inform Jack the only match for a bait and switch operation is Kim Bauer. Chase tracks down the man who escaped the hotel quarantine. Palmer informs his cabinet on the dangers of the threat.
Jack works on using Saunders' daughter in an attempt to gain control of the virus. Michelle waits to find out if she's infected. Palmer navigates around a angry and confused press. Saunders starts making demands on Tony.
Tony works covertly to find a way to get Jane Saunders out of CTU and deliver her to Saunders before Jack and Chase find him. Senator Keeler receives some damaging information on President Palmer from a surprising source.
Jack and Tony clash as they wait for the time of hostage exchange with Saunders. Senator Keeler confronts President Palmer about the Milliken cover-up while Wayne initiates a secret operation against Sherry.
Jack and Chase corner Saunders' henchman Arthur Rabens in an active public school. Tony faces losing command of CTU and treason charges for saving Michelle. An emotionally broken President Palmer decides to drop out of the race for reelection.