Self-injurious behavior typically occurs in response to specific antecedent stimuli that predict the occurrence of such desirable consequences of the behavior as obtaining attention from others, escaping aversive situations, and securing preferred foods, objects, and activities. Setting events constitute an additional controlling variable, altering the probability that a specific antecedent stimulus will evoke self-injury. We discuss the influence of several biological factors, including menses, otitis media, fatigue, allergies, and constipation, that may serve as setting events. We also present a model which suggests that these events alter the functional properties of the antecedent stimuli that control self-injurious behavior, thereby strengthening the specific consequences that maintain the behavior. One implication of this model is the likelihood that effective intervention will have to have multiple components, addressing both the biological and environmental variables that control the behavior. A second implication is that greater collaboration between medical and psychological or educational practitioners will be necessary in order to address the multiple factors that affect self-injury. © 1995 Wiley-Liss, Inc.