She and Peter Parker used to be a relationship, but she left him due to the stress of knowing that he was Spider-Man. She eventually felt bad for walking out on Peter and went to visit him. She came upon Peter having a nightmare, and he accidentally knocked her back with his super strength. Peter woke up and apologized for hurting her. Mary Jane in turn apologized for walking out on him and realized that she needed to be there for Peter as a friend. As Peter told her that he was unraveling, she asked him about his strange new suit. Peter agreed with her that he needed to get it examined.
Mary Jane later visited Peter at his apartment when he didn't show up for his Aunt May's funeral and wasn't answering his phone. She was shocked to find him hanging from tendrils in midair. Mary Jane said that the papers were all saying that Spider-Man was a killer and asked if it was true. Peter answered that it was true and expressed his desire to kill criminals so no one else like Aunt May got hurt, much to Mary Jane's horror.
Later, Mary Jane met with Peter's other girlfriend Black Cat in Peter's apartment to discuss the situation with Peter and got into an argument that was interrupted when Peter was brought in by J. Jonah Jameson. Peter was no longer bonded with the black suit after a battle with the Sinister Six. However, when Peter killed the Kingpin, he ensured the world learned that Peter was Spider-Man. Consequently, the NYPD surrounded Peter's apartment to arrest him for his crimes.