Having left New York in the care of Ben Reilly, Peter and Mary Jane have started a new life in Portland, Oregon, where Peter works as a research scientist. A top-secret unorthodox experiment at the lab where Peter works results in disaster! When he discovers that he has inadvertently contributed to this experiment, Peter feels duty-bound to don his costume one last time and solve this new crisis. But he is torn between his promise to Mary Jane that his web-slinging days are over, and his sense of responsibility.