Thousands of years ago, a hunter was captured by the Kree Reapers and, during their experiments on his DNA, was infused with their blood; he became known as Hive in the present. Telling his origin story to Daisy Johnson, Hive explains to Kirk Vogel and the other two heads of HYDRA who escaped capture that he will duplicate the experiment on them, changing them into Inhumans.
At the Playground, Lincoln Campbell grows restless with his inability to help to find Johnson, so he volunteers to be the guinea pig for the antidoote that Leo Fitz and Jemma Simmons have concocted against Hive's sway.
Meanwhile, Phil Coulson has watched hours of satellite footage until facial recognition has found Johnson in south Wyoming in a town once owned by Gideon Malick. Coulson is cautious that this is a trap, but Alphonso Mackenzie believes that Johnson wants to be rescued. Coulson tells Mackenzie that he and Melinda May will lead a team to the town, not to save Johnson, but to kill Hive.
In Union City, Holden Radcliffe does his experiment to change the three HYDRA leaders; their skin melts off the bone. Radcliffe promises to do better, saying he failed because he does not have the DNA of a living Kree. Radcliffe assures that everything he has done his whole life was practice towards jumpstarting Humans to this new phase of evolution; Hive acquiesces, sparing Radcliffe's life.
Four volunteers, including Agent O'Brien, go with Mackenzie and May to Union City; their order is to kill Hive and leave, while unnecessary contact with any other Inhuman should be avoided.
Fitz is uncomfortable disagreeing with Simmons since they are in a relationship, but he sides with Campbell that the experiment is worth the risk; however, Coulson casts the final decision and opts not to proceed. Campbell waits until the others leave and proceeds nonetheless.
May pretends to be a HYDRA agent and gets Hellfire boasting and flirting; she learns Hive's plan to change all of humanity. As night begins, the agents learn of Hive's location, but before they can attack, the Kree Reapers come to Earth since Hive had summoned them.
The agents watch as the Reapers kill Alisha Whitley, but when Johnson attacks one, and wins by breaking his bones, Mackenzie goes to rescue her. The two argue until Johnson rejects Mackenzie's offer to return to S.H.I.E.L.D.; Mackenzie then uses a Splinter Bomb to destroy the living Kree that Johnson had captured. Johnson beats Mackenzie constantly and angrily uses her powers on him.
Meanwhile, the other Reaper fights Hive, as May and the other agents watch. Their battle is intense and prolonged until Hive uses his parasites to destroy the Reaper's face. Coulson then calls the order to attack, but the best weapons of S.H.I.E.L.D. do little against the dark Inhuman. They gather the gravely injured Mackenzie and evacuate.
Campbell learns that the antitoxin is a failed experiment.
Hive shows Johnson the heart of the Reaper he killed and reprimands Johnson for allowing her former friends to stop his progress. Johnson reveals that she has Kree blood inside her and she is willing to let him have it.
- Clark Gregg as Phil Coulson
- Ming-Na Wen as Melinda May
- Brett Dalton as Hive
- Chloe Bennet as Daisy Johnson
- Iain De Caestecker as Leo Fitz
- Elizabeth Henstridge as Jemma Simmons
- Henry Simmons as Alphonso Mackenzie
- Luke Mitchell as Lincoln Campbell
- John Hannah as Holden Radcliffe
- Axle Whitehead as JT James/Hellfire
- Derek Phillips as Agent O'Brien
- Alicia Vela-Bailey as Alisha Whitley
- Alexander Wraith as Agent Anderson
- Mark Atteberry as Kirk Vogel
- Briana Venskus as Agent Piper
- Lynn Longos as Ex-HYDRA Follower #1
- Chris Hubbard as Ex-HYDRA Follower #2
- Jason Glover as Mayan
- Erol Brandis as HYDRA Agent (uncredited)
- Union City, Wyoming
- S.H.I.E.L.D. Academy (mentioned)
- South Dakota (mentioned)
- Brisbane, Australia (mentioned)
- Central America (flashback)
- Phil Coulson's Prosthetic Hand
- Kree Battle Axe
- Kree Orb
- Splinter Bomb
- Iron Man Armor (mentioned)
- Super Soldier Serum (mentioned)
- GH.325 (mentioned)
- Gideon Malick
- Grant Ward
- Will Daniels
- Iron Man
- Captain America
- Bobbi Morse
- Lance Hunter
- Calvin Zabo
- Ruben Mackenzie
- Ian Quinn
- Crocodile Dundee
- Ted Kaczynski
- Ziggy Stardust
- Papa Smurf
- Hive's plan to turn the world's population into Inhumans bears a resemblance to Magneto's plan in the first X-Men film.
- Similarly, the deaths of the HYDRA heads resemble that of Robert Kelly in the film.