Participants were 109 adults with severe intellectual disabilities and long histories of psychotropic drug use. Side effect profiles were examined in the context of types of mental health disorders observed using the Diagnostic Assessment for the Severely Handicapped-Revised (DASH-II) and the Behavior Problems Inventory-Revised (BPI-01). The best predictor of severe side effects were challenging behaviors, especially aggression and to a lesser degree self-injurious behavior. The implications of these data for current and future practice are discussed. (Contains 7 tables.)