Armored car driver Paul Blankenship is coughing up blood, but he tells his wife it's nothing. After checking a syringe in his pocket, Paul makes his way into the restroom at Westland Bank to find blood dripping from his ear. He calls 911 - not for an ambulance, but to record a goodbye message for his family - then passes out. The responding EMTs quickly put the entire building under quarantine.
After confessing the story of Tom to Ressler, Liz calls in the FBI and tells them them the whole story too. She's surprised to learn Gina Zanetakos escaped two weeks ago. Meanwhile, Tom is on the run, still being tailed by Red's men. Tom catches the tail, a man with a spider tattoo on his neck, and forces him to tell Red he lost his mark. Red proceeds to Cooper's office, where Liz tenders her resignation; despite Red's news of an urgent case, she's no longer willing to speak to him. Red pushes, claiming many people will die, so Liz caves, agreeing to work on one last case. Paul Blankenship, now dead of the Cullen virus, which could lead to a global pandemic, was a foot soldier in a mastermind's nefarious plan - a plan to kill Red.
Liz and Ressler find the CDC's Dr. Nina Buckner at the bank. She explains Cullen is so deadly there's a moratorium on researching it and all known strains are on lockdown. It looks like the strain Blankenship had was designed only to infect the original host without spreading; they found a syringe in his jacket. Since few people in the world are able to design such a virus, Liz climbs on Red's jet to visit his old friend. Liz is unwilling to talk to Red at all, so he hands her the copy of Tom's codebook as an olive branch. Meanwhile, the CDC has discovered the syringe Blankenship carried contained the virus' antidote, and his text messages reveal he was being blackmailed into doing something. Rather than carry out his task to receive more of the antidote, he chose to die. Elsewhere, another armored guard, David Klein, receives a distorted video message from a man he doesn't know, Dr. Nikolaus Vogel. Now Klein is infected with Cullen. He'll be supplied with antidote treatments lasting 24 hours, as long as he follows orders.
Liz is disgusted to learn Red's old friend, Dr. Bruce Sanders, the country's foremost expert on virology, is a delusional mental patient, who keeps harping on Space Agent UD-4126. According to Sanders, Cullen is the harbinger of the apocalypse. Once Sanders hands over a stack of research on Cullen, Liz heads for the airport by herself, angry that Red diverted them to the mental hospital so he could get her alone to try to bring her around. She tells Cooper she's ready to arrange a meeting with Red so the FBI can take custody of him. Back at the Post Office, Cooper meets with Agent Martin. If Keen walks, the task force will be disbanded, and Red will no longer have immunity. It's time to bring him in. Sanders' research comes back from Buckner: Sanders has synthesized an antidote to Cullen, which means he's been working with someone on the outside with lab access. When Sanders refuses to speak with Liz, she finds Red in Bryant Park and asks for help. He hands over a bloody piece of flesh with a spider tattoo - a message from Tom.
Back at the mental hospital, a confused Sanders continues to harp on UD-4126. On a whim, Liz has Aram research badge numbers, coming up with a hit on the CDC's Dr. Nikolaus Vogel. In Vogel's basement, Ressler and Meera find a state-of-the-art lab and a tray of syringes containing the antidote. During interrogation, all Vogel will say is "He's coming." After learning Vogel has infected five people from all walks of life, Liz plays hardball - she has infected him and is happy to blackmail him using the antidote to get the five names. While waiting for him to talk, Liz gets busy, working with Tom's codebook. Hours later, she rushes back to the Post Office, convinced most of the names on Red's Blacklist are connected - and they all trace back to Berlin. Berlin is a person, he's after Red - and Red doesn't know who he is.
Vogel eventually gives up his five, who all work at airports and are involved with a prison transport plane. Liz tells Cooper she may have acted too hastily with respect to Red, but he tells her it's too late. As Vogel's plan unfolds and a Russian pilot takes over a prison transport plane over American airspace, Liz returns to Bryant Park to find Red, then begs him to get into her car. She admits she set him up to be taken into custody, and his immunity is gone. But rather than rush away, Red sits down, wanting to know more about Liz's change of heart. Knowing the air force has scrambled jets with shoot-to-kill orders, a figure on the plane orders the pilot to land. Liz tells Red she knows about Berlin - now she needs answers, and she needs Red to get those answers. Claiming the worst thing that could happen would be losing Liz, Red pulls out a gun, so the descending FBI agents won't think they're in cahoots. Handing Liz his gun, Red gets on his knees, assuming the same position he did when he first turned himself in to the FBI. That's when the Russian plane sails overhead and crashes nearby.