Atypical antipsychotic medications for self-injurious behavior (SIB), aggression, and destruction among people with mental retardation and development disabilities are becoming increasingly accepted. Most studies are on risperidone and fewer have been conducted on clozapine. The present single-blind study reports marked reductions in SIB and aggression of two persons with profound mental retardation who were nonresponsive to all other behavioral and psychopharmacological interventions, including risperidone. The most effective dose was 200 mg/day. Side effects were mild and the drug was tolerated well.