While driving through the desert at night, KITT wakes up Mike, sensing that he's still exhausted from his last mission. KITT has uploaded files for another mission, so Mike pulls over so he can access them from KITT's hood. KITT is worried that Mike will miss a big event with Sarah if he takes the mission.
The next day, a Courier walks through a mall with a briefcase as everyone at HQ looks on. A pair of unknown agents follows the Courier as he drops his briefcase and keeps going to divide them. KITT loses the video signal when the Courier disappears behind a locked door to hand off a small box to a guy only known as Ben.
Ben punches the Courier and loads him to the back of a van, which drives off by itself. Ben cuffs the amazed Courier, then pulls off his mask - it's Mike, and the van is really KITT. KITT asks if he can transform as well, and Mike consents, as long as KITT is positive that no cell phone camera will record it.
Back at HQ, Mike tosses Rivai the Courier's box, as the Courier explains that he has another pick-up to make, and refuses to grant a voice sample. Mike throws him in KITT and lets the gimbal gyrate wildly. With his brains tossed, the Courier complies, allowing Zoe to perform a retinal scan, while Mike searches his Blackberry.
Sarah appears in a stunning dress. Mike promised to accompany her to a friend's wedding later that evening, and he thinks Sarah will be mad that he has a mission, but she's not. All she wants is one dance, and the wedding is five hours away. Mike promises to try to make it. KITT doubts it can happen, so Sarah tells him to have faith.
KITT warns Mike that they only have 34 minutes to make the Courier's pick-up, so he jumps in the car. On the way, Mike puts in contact lenses made to match the Courier's, and a voice modulator that affixes to his larynx, which makes his own voice match the Courier's.
Armed henchmen bring Mike to meet Walton Ash, who immediately makes Mike undergo a retinal scan and voice confirmation. As one of the henchmen hands over a case, he jams a hypodermic gun into the nape of Mike's neck. Ash explains that he is guarding Mike's loyalty by poisoning him. If he doesn't make the drop on time, he won't get the antidote.
Sarah already has Mike's blood analysis underway as he pulls back into the SSC. She gives the already woozy Mike a general inhibitor to slow the effects of the poison. Mike has been given a cocktail containing mostly Hyoscine, which acts like a truth serum. Billy opens the case, which contains a pass to the Tech For Tomorrow symposium and a coat check ticket.
Rivai promises Mike that she will meet him at the drop point with a team; he just has to get visual ID on the recipient, so she can track and retrieve the antidote. KITT estimates that Mike has about two and a half hours before the poison ends his life.
Mike brings the briefcase to a park, then gets woozy, missing the beautiful girl who picks it up. She takes Mike's picture and runs to her car, so Mike and KITT give chase. The girl collides with a semi, and is killed in the crash. Mike pulls a ceramic gun and her laptop out of the wreckage.
Rivai determines that the girl was an assassin, and her laptop indicates that once she confirmed her target, $10 million would be wired to her bank account. She figures that if Mike makes the hit disguised as Ben, she can use the laptop to trace the deposit and find Mike's poisoner. Billy makes paint bullets for the gun so Mike won't have to kill anyone.
Deteriorating, Mike tells Sarah that she's beautiful, then falls over. Sarah slaps him back to life and helps him into KITT. At Tech for Tomorrow, Mike makes it past the metal detector to pick up a purse at the coat check. The purse contains special contacts which act as a tracking system to identify the target, Damien Richards, the visionary founder and CEO of Innovative Technologies.
Mike has to rip off his Ben mask to put in the contacts. Close to the end, Mike pulls the trigger and runs off, as Rivai and Zoe descend to assure Damien that he's really okay. Disguised as a police car, KITT directs Mike to escape through the kitchen, then redirects the cops to another location, allowing them to drive off.
After deleting all surveillance footage of Mike shooting Damien, KITT informs him that Damien has hired an offshore company to short sell his stock; Damien's death would make stock prices plummet. Mike orders KITT to find out who's behind shorting the stock, as the story of Damien's death is broadcast all over the news.
Torres asks Sarah if she's told Mike that there's no antidote yet, but she figures that he's already guessed. When she asks Torres if he's just going to let Mike die, he sends her off to help him. Meanwhile, KITT identifies the man behind the stock shortage: it's Ash. KITT transforms to Attack Mode and plots the interception of Ash.
Mike contacts Sarah, who's on her way. He apologizes, tells her that he loves her, and keels over. KITT tells Sarah that Mike is dead, just as they cross paths. Sarah rushes to defib Mike and implement CPR, but nothing's working, and the defib won't recharge quickly enough. KITT tells Sarah that he can apply the correct voltage, and brings Mike back to life.
Sarah loads Mike back into KITT, but he passes out again, so she stabs him with an Epi-pen from KITT's onboard pharmacy. Ash is heading to a parking garage, planning on boarding a helicopter which is presently hovering overhead. KITT gives chase, as a guy shoots at him with explosive bullets that damage KITT's nanoskeleton. Sarah orders KITT to deploy his grappling hook, which hits its mark, ripping off the rear axle of Ash's SUV.
Mike passes out again. On the roof, Rivai and her team descend upon Ash, insisting that he hand over the antidote. When he hesitates, Sarah rips out her gun, promising to shoot him right now. He pulls a bottle out of his jacket, but lets it fall to the pavement. Sarah soaks a little of the antidote up with her shirt, then orders KITT to analyze it.
Working together, Sarah and KITT come up with a serum that may or may not save Mike's life; they'll just have to have faith. Sarah injects Mike, and everything fades to white...
Sarah and Mike recuperate on a beach. Could this be heaven? It's not, because if it was, Torres wouldn't be calling. Sarah teases Mike that he should get poisoned more often, since it seems like the only way to get a day off. Some day, she'll tell him what he said. Sorry that he missed the wedding, Mike offers a dance, which is interrupted when Torres has KITT patch him through; it's time to go back to work.