Ethan Hunt (Tom Cruise), while vacationing, is alerted by the IMF that someone has used his identity to assist Russian bio-chemical expert Dr. Vladimir Nekhorvich (Rade Serbedzija) of Biocyte Pharmaceuticals to enter into the United States, but purposely crashed the commercial airliner en route. Nekhorvich, an old friend of Ethan, had forewarned the IMF of his arrival, planning to deliver a new virus called Chimera and its cure,Bellerophon, both of which he was forced to develop by Biocyte, into the IMF's hands. With the crash of the plane, IMF is worried that the virus is out in the open, believing that IMF agent Sean Ambrose (Dougray Scott) is behind the incident. IMF assigns Ethan to recover it. Ethan is told that he can use two members of his team to help him, but the third person to help him must be Nyah Nordoff-Hall (Thandie Newton), a professional thief presently operating in Seville, Spain as she will be able to get close to Ambrose, being an ex-girlfriend of his.
After recruiting Nyah, Ethan meets his team, computer expert Luther Stickell (Ving Rhames) and pilot Billy Baird (John Polson) in Sydney, Australia, where Biocyte laboratories are located along with Ambrose's headquarters. As Ethan and the others stake out Biocyte, Nyah gets close to Ambrose and begins to find any information related to the Chimera virus. At a horse racing event, Ambrose quietly meets with Biocyte's CEO, John C. McCloy (Brendan Gleeson), and shows him a video of the Chimera virus affecting one of Nekhorvich's colleagues taken from Biocyte, using the footage to force McCloy to cooperate with them. Nyah is able to steal the video footage long enough to transfer it to Ethan and his team, who learn that the Chimera virus has a 20-hour dormant period before it causes death through mass destruction of the victim's red blood cells. This is depicted through several increasingly graphic pictures, which show the victim dead after 37 hours. Bellerophon can only save the victim if used within the 20-hour window.
The IMF team kidnaps McCloy and learns that Nekhorvich had actually injected himself with Chimera, the only way he could smuggle the virus from Biocyte, and had all the known samples of Bellerophon, now presently in Ambrose's hands. Ambrose has blackmailed McCloy to sell him the virus for £37,000,000 and promising to return the samples of Bellerophon. Ethan's team plans to break into Biocyte and destroy the virus. Ambrose, posing as Ethan, tricks Nyah into revealing Ethan's plan. Ambrose secures Nyah and prepares to raid Biocyte himself to secure the virus. Ethan is able to destroy all but one sample of the virus before Ambrose interrupts him, and an ensuing firefight begins. Ethan learns that Ambrose is holding Nyah and stops firing, during which Ambrose orders Nyah to retrieve the last sample. When she does so, she injects herself with it, thus preventing Ambrose from simply killing her to get it. As Ambrose takes Nyah, Ethan escapes from the laboratory and starts a 20-hour countdown before the virus takes over Nyah's body.
Ambrose opts to let Nyah wander the streets of Sydney in a daze, and orders McCloy to effectively hand over enough control of Biocyte to make him the majority shareholder, or else Nyah's infection will cause a pandemic that will kill 17 million people in Australia alone; Ambrose's plan is to make a fortune when prices of Biocyte's stock skyrocket due to demand for Bellerophon. Ethan's team is able to locate and infiltrate the meeting, stealing the samples of Bellerophon while taking out many of Ambrose's men. Luther and Billy locate Nyah who has wandered to a cliff side, intent on killing herself to prevent Chimera from spreading. As the two IMF agents bring Nyah to Ethan, he and Ambrose engage in a fist fight and wilds out on Ambrose. With little time left on the 20-hour countdown, Ethan finally gains the upper hand over Ambrose and shoots him dead, and then Luther injects Nyah with Bellerophon. Ethan reports to IMF on the successful mission. IMF clears Nyah's criminal record, and allows Ethan to continue his vacation with her in Sydney.
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