Peter Parker got the alien costume in the planet Beyonder created, during the Secret Wars, while trying to fix his damaged uniform. The new costume did a lot of tricks, like firing it's own webbing. By the time, Spidey was romantically involved with the Black Cat, who had gained powers sponsored by the Kingpin. While Peter slept, the costume binded to him and took him swinging through the city, without him realising. Every day he woke up more and more tired. Reed Richards eventually discovered what the costume really was, an alien symbiotic organism, who fed off the adrenalin of the host, and he was able to prevent him from binding with Peter permanently, using the symbiote's vulnerability to some sound frequencies.
Eventually, the symbiote escaped and tried to bind with Peter one more time, but Peter managed to get rid of him by sacrificing himself under a church's bells. The sound-vulnerable symbiote had to leave his host or die by the bells' toll, but it also dragged an uncounscious Pete away from the bells before leaving. In the future, the symbiote would bind to Eddie Brock and form one of Spidey's greatest nemesis (arguably the greatest physical one), Venom.
The story starts with Spidey and Black Cat making out after he returned from Beyonder's planet. They both realize Peter isn't very well, and Peter goes to Fantastic 4's H.Q. searching for Reed, but he finds nobody. Going to Curt Connors, he does some physical tests, but he finds no reason to Spidey's fatigue. Days later, Spidey returns to the F4, to hear the bad news. But in this reality, the sonic blast doesn't break the bond between the creature and the host. The Symbiotic Spider-Man's mind is now controlled by the creature, and Reed has no other choice than to shoot it point blank with the sonic gun in its max power, which KO's Spidey, but doesn't split the bond.
Science and magic fail to sever the connection between Spidey and the symbiote, as both Reed Richards and Doctor Strange realise that their knowledge has been useless so far. The symbiote claims that he and Spider-Man are now one, and no power in the Universe can split them apart, and takes the opportunity to escape, as his captors are concerned with what to do next. Due to his Spider-Sense and the symbiote's camouflage powers, the Symbiotic Spider-Man was able to remain undetected by Richards for days. Meanwhile, Peter tried to call Felicia Hardy, but the symbiote's control kicked in while he was talking, informing her that Spider-Man was no more. She storms at Reed Richards for not searching for Spidey, and out of hate and spite, robs an auction house to give some gems to the poor... Huh?! Where did that come from? Anyone sees some sense in this?
Days later, the SHIELD agents die, as no Spidey is there to save them. A rampaging Hulk battles Thor while Strange tries to send him to an alternate plane, until they realise how to reverse the doing of Nightmare, Strange's foe, who caused Hulk's insanity. But before the Hulk falls through the dimensional gate, Symbiotic Spidey shows up, KO's Strange and the symbiote leaves Spidey for the Hulk. As the Wasp approaches Peter, she sees the body of an 80-year old man pleading for help. The Avengers try to overwhelm the symbiotic Hulk, but since Hulk's mind is weak, the symbiote quickly takes control over Hulk's power, thwarts the Avengers and flees.
At the Avengers' mansion, Thor stands by Peter's bed, while Peter explains that the symbiote feeds on human adrenalin, specially from super-beings. That's why it always kept Spidey on the move. When the adrenalin source was almost depleted, it abandoned him for the Hulk. Black Cat says that they must kill the monster, and Thor reasons that doing so would kill Bruce Banner. While Black Cat claims it doesn't matter, justice should be done, Peter isn't giving much thought to that. He has lost 50 years of his life.
A week later, Peter visits his his aunt's house. He introduces as Harrison, from the Bugle, and says that Peter talks a lot about her, that he loves her very much, and that Peter will return, to have faith. Then he leaves, as May and MJ hold each other. MJ realises that one of Spider-Man's enemies must have finally achieved his goal.
Next morning, in the Avengers mansion, Reed knocks on Peter's door, to compare their notes on the symbiote. He finds Peter Parker lying on the floor, dead of old age. The World's greatest heroes grieve at Spider-Man's funeral, with Johnny Storm speeching, Black Cat watches over at the grave's feet, and while all the heroes are sad, Thor is down on one knee, apparently crying. As everybody leaves, Black Cat remains. Hours pass, and the Kingpin arrives, to pay his respect to a valuable Man. Then, they leave together.
At the F4 H.Q., after examining Peter's notes for the last days, Reed concludes that Peter was a genius, who could have had a great future ahead. Adding them to his own, he built a tracking device and a weapon to kill the entity. The Avengers, the F4 and Doctor Strange trace the signal to Mount Rushmore, where they split to find the symbiotic Hulk. It's Thor that finds him, and after they fight, the symbiote leaves Banner's body, and overtakes Thor, claiming to have all the powers of his hosts. Thor's attempts to resist only weaken him, and the heroes watch symbiotic Thor enter a cave, to complete the binding, promising that he'll exit it to kill them soon. Richards has one last plan before using the weapon. He summons Blackbolt, the leader of the Inhumans, who enters the cave, and while a desperate symbiotic entity attacks in fear, he screams. When the dust settles, there is no more Mount Rushmore, and Thor rises battered, with the symbiote lying on the floor. It was still vulnerable to sound. The symbiote was still alive, though, and while Strange was trying to send him to the same dimension he tried to send the Hulk, Black Cat shows up, with a gun identical to Reed's, and she kills the creature. She vents her anger on the heroes, telling them that they'll never know the price she paid to have justice being done.
She had given a copy of Peter and Reed's notes about the weapon, and gave them to the Kingpin. She got her weapon, in exchange for a life of criminal service...
#48 on Wizard Magazine's "100 Best Single Issue Comics Since You Were Born" list.