Mary Jane, thinking that Peter might be at the Daily Bugle, stops by and runs into John Jameson, who gives her a weird vibe. She pretends to have to go and takes off. As she leaves, she unknowingly drops her scarf, which is picked up by John.

Peter, as Spider-Man, is out on patrol when he gets a disturbing phone call from Dr. Connors, who appears to be on the verge of transforming into the Lizard. Spidey swings towards Connor's apartment but arrives a few seconds too late, as both Connors and his son, Billy, are transformed into lizards.

In Sensational Spider-Man #24, Spider-Man confronts the two lizards and, during the ensuing battle, gets hurt quite severely. He flees to the rooftop, the lizards in tow, where he runs into the Black Cat. As if suddenly possessed by a wild animal, the Black Cat savagely attacks the Doctor-Lizard while the Billy-Lizard attacks Spidey. The Black Cat fares well and sends her opponent off the rooftop. Spidey has a rather difficult time with the Billy-Lizard; however, he gets unexpected (and unwanted) help when a nosy neighbor armed with a rifle shoots the Billy-Lizard. At issue's end, the Billy-lizard has transformed back into his human self and he is bleeding to death from his gunshot wound.

While all this takes place, Mary Jane gets an unexpected visit from John Jameson, who is bringing back the scarf she accidentally dropped at the Daily Bugle in the previous issue. MJ feels uneasy about letting him in Avengers Tower but Aunt May invites him in for tea and biscuits. On his way in, John attacks the doorman in the lobby for drinking on the job. He then makes his way up.

This issue also marks the long-awaited return of Vermin who unwillingly comes to the aid of a prostitute by killing her crooked cop-pimp and feeding on his flesh.

In Sensational Spider-Man #25, Spider-Man, accompanied by the Black Cat, takes Billy Connors to the Fantastic Four Headquarters to get help from Susan and Reed Richards. Billy is immediately put inside some kind of bio-bath and while he recuperates, Reed performs tests on both Spidey and the Black Cat to determine why they, like so many others, have been experiencing bouts of extreme anger.

Meanwhile, at Avengers Tower, John Jameson transforms into the Man-Wolf and attacks Mary Jane and Aunt May. Thankfully, they manage to lock themselves in the kitchen and activate the defense system. Several blocks away, Spidey senses that MJ and Aunt May are in danger and rushes back to their rescue, leaving the Black Cat to be further probed. When he arrives at the tower, MJ and Aunt May have already been saved by a herd of Iron Men who were alerted by the distress signal sent out when the defense system was activated. Peter/Spidey is left wondering what just happened.

Somewhere in the New York City sewers, the Lizard, recovering from his skirmish with the Black Cat, is tormented by memories of injecting his own son with a bio-restorative serum, as "told" by the meteor rock he was called on to study in Sensational Spider-Man #23. He lets out a roar that echoes through the sewers and reaches the ears of Vermin, who is feasting on the crooked cop-pimp he murdered in last issue. Vermin lets go of his victim and takes off towards the Natural History Museum. The Lizard takes off in the same direction. Meanwhile, back at the Fantastic Four Headquarters, the Black Cat takes off through a window, having had enough of being poked and probed.

At issue's end, Peter, as Spider-Man, takes off into the night and goes to meet the one person that can provide him with some extrasensory help: Madame Web.

This is where this issue picks up.

ACT 1: Spider-Man visits Madame Web who pretty much says nothing useful except suggesting that he chase after his friend, Dr. Curt Connors, a.k.a. the Lizard, where nature is thickest, and follow him to the source of the "infection". Realizing that she must mean Central Park, Spidey heads in that direction.

ACT 2: Several blocks away, the Black Cat comes to rest on a rooftop, anger boiling in her veins, her guts on fire. She tries hard to fight it off but is having a rather difficult time. On cue, the Puma shows up and tells her not to fight it and to fight him instead. The Black Cat asks him how he knew how to find her and he explains that he tracked her for thirteen blocks. He then tells her to release her fear and anger before she does something terrible. She refuses but he stubbornly forces her to attack him. And she does, which seems to relieve the pressure off her shoulder. Puma is unharmed from the assault and explains that whatever is doing this to them, it builds up in their systems and the only way to get rid of the anger is to act on it.

ACT 3: Meanwhile, back at the Fantastic Four Headquarters, Reed Richards has conducted some experiments on the recently captured John Jameson and has come to the conclusion that something radioactive has been affecting him, as well as so many others. What Reed discovered is that the protoreptilian brains of those affected have become enlarged and have begun taking over functions normally controlled by their cerebrums. In turn, this is causing enzymes to be released from their hindbrains and into their bodies, triggering waves of anger and causing them to transform into their monster counterparts.

ACT 4: Puma explains to the Black Cat what happened to him earlier that evening when, as Thomas Fireheart, he had to quickly get out of a board’s meeting, as he was starting to transform into the Puma, and headed into a back alley where he murdered a poor innocent mutt to satisfy his hunger. He continues explaining that, after that took place, he started heading uptown and picked up her scent on the way. The Black Cat comments that she too was heading uptown, though she does not know why. Puma replies that they are being drawn there.

ACT 5: The Lizard makes his way into Central Park, completely unaware that he is not alone. On cue, Vermin jumps down from a tree and attacks him. The ensuing battle is brutal and blood is spilled viciously. Just then, Spider-Man arrives on the scene and jumps in the mêlée. For a moment, Vermin and the Lizard join forces, though probably unknowingly, and tackle Spidey into a nearby lake (it is revealed that Spidey had planned for this to happen). While Vermin and the Lizard struggle with each other, Spidey uses his new appendages to extract himself from the lake. As he surfaces, the Lizard and Vermin in tow, he stops dead in his tracks, having found the source of the infection, as Madame Web put it: Dr. Vincent Stegron.

To be continued.