The mechanisms and applications of the activity-stress (A-S) research paradigm are examined in this article. Past research has reflected the value of this paradigm in the investigation of ulcerogenesis. Evidence is offered to support a theory explaining the excessive running observed in the A-S animals, according to which, animals commence running to increase body temperature after failing to adapt to the restricted feeding regime. Further, excessive running levels are hypothesized to be sustained by reinforcement resulting from increased mesolimbic dopaminergic activity. Finally, parallels between the behavior observed in the A-S animals and some forms of maladaptive behavior observed in humans are discussed.