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When Peter's clone, , appeared. discovered that she was pregnant. While she experienced some complications in her pregnancy, Reilly's scientist friend Seward Trainer helped her. Peter and Ben were told by Trainer that Ben was the real Peter Parker, and Peter was the clone (which later proved to be a lie). Peter, acting on hypnotic suggestion by the Jackal, attempted to kill Mary Jane, but was prevented by Ben Reilly (as the Scarlet Spider), his teammates the New Warriors, and Kaine. Later, while arguing with Ben, Peter accidentally struck Mary Jane. After this, he decided to quit as Spider-Man, because the stress of his double life was endangering his wife and unborn child.

Peter and Mary Jane left New York and moved to Portland, Oregon. While there, he lost his powers in a lab accident. They lived there peacefully for several months, adapting happily to normal life. However, they missed New York City and their friends, and moved back. Peter became unexpectedly ill and nearly died, but instead regained his powers. During the Onslaught crisis, Mary Jane was scanned by a Sentinel robot, who detected genetic abnormalities in her fetus.

Soon afterward, when Mary Jane's baby was already past due, she was poisoned by Alison Mongraine, an agent of the Green Goblin. Mary Jane's baby was stillborn. The baby has not been seen since in the normal 616 continuity, but appears in stories set in the alternate-timeline MC2 universe. In this timeline, Mary Jane and are reunited with their child by Kaine. Two years later, Peter loses his leg in a final confrontation with The Green Goblin. Years later, Mayday becomes the heir to her father's legacy as Spider-Girl the symbiote attempts to re-bond with Peter Parker but is forcefully bonded instead to Spider-Girl's friend Normie Osborn III, the grandson of the original . It takes control of Normie, but when it also attempts to absorb Spider-Girl, their combined force of will defeats the creature. Instead of destroying it, Normie keeps the symbiote and allows it to bond with him, purging the symbiote of its violent and aggressive emotions. In Spider-Girl #100, Normie transfers the symbiote to a critically injured Spider-Girl whom was stabed so it can heal and save her. The symbiote later sacrifices itself to save Spider-Girl's life by confronting a sonic-weapon armed.