When Spider-Girl stumbles on to a S.H.I.E.L.D. mission that’s about to go bad, she inadvertently sets free the deadliest (and most requested) foe that Spider-Man ever faced — Carnage!
In Brooklyn, Arthur Weadon is observing his new team of super-powered individuals with Maria Hill of S.H.I.E.L.D. His program involves rehabilitating convicted super-villains and allowing them to serve prison time serving the government. His new members include Earthshaker, Mr. Abnormal, and Killerwatt. The team leader is the former assassin, Kaine. Hill tells Weadon that her superiors have a mission for them regardless if he thinks they're ready or not.
Spider-Girl is web-swinging her way to school. She is on cloud 9 now that she has her parents blessings to continue to be Spider-Girl and also because her father has made more web-fluid for her. Arriving at school, her friend, Courtney is determined to find out why her boyfriend, Moose, hasn't been calling her since he's moved in with his uncle. She doesn't know that his dad has been diagnosed with cancer. She also found out that he's going to be the Midtown Medical Center. It turns out she skips class to go see him.
In Manhattan, Kaine speaks with Darkdevil about the mission. He wants someone he can trust to watch his back. Darkdevil asks if he's going to bring in Spider-Girl since the route they're taking, delivering something called Specimen 297, will be going through her "territory." Kaine says, absolutely not. Between the two of them and their contacts, they were unable to get any information on what Specimen 297 is.
At the Parker home, Mary Jane receives a call from May's vice-principal, Mr. Slattery. He offers her a job at Midtown High. In the background, little Ben is seen trying to shake off a toy block that seems to be stuck to his hand...
At the hospital, Courtney finds where Moose is. He is in his father's room with his arm around another girl. When Courtney sees this, she runs away in tears before Moose can say anything to her.
May is walking home from school, deciding to try to go to the hospital to catch up with Courtney. Suddenly her spider-sense goes blazing. She senses some danger from below. The armored vehicle transporting Specimen 297 is attacked. In the confusion, some men take the specimen. This makes Mr. Abnormal upset as his ego is being pushed with someone stealing from him.
A fight over Specimen 297 erupts in the sewers. The team of reforming villains is getting beat when Spider-Girl arrives to turn the table. She manages to get the sphere containing Specimen 297 away from them. As they begin shooting at her, she drops the sphere, which crashes into the wall. Her spider-sense really goes haywire. The men try to take advantage of her distraction to no avail. Soon, the leader reveals herself to be the Contessa Valentina Allegro De Fontaine. This was apparently a S.H.I.E.L.D. top secret mission.
An agent rushes to the Contessa to tell her that the sphere was damaged during the fight. What was inside is now gone. She tells Spider-Girl that it was a living weapon that was thought to have been destroyed a decade ago. It was secretly being studied by the government in secrecy.
A red symbiote is seen emerging from the sewers. It seems to attack a person wearing a Midtown jacket. Carnage has been reborn!