OBJECTIVE: Violent behavior among individuals with severe mental illness has become an important focus in community-based care. This study examines the joint effect of substance abuse and medication noncompliance on the greater risk of serious violence among persons with severe mental illness. METHOD: Involuntarily admitted inpatients with severe mental illness who were awaiting a period of outpatient commitment were enrolled in a longitudinal outcome study. At baseline, 331 subjects underwent an extensive face-to-face interview. Complementary data were gathered by a review of hospital records and a telephone interview with a family member or other informant. These data included subjects' sociodemographic characteristics, illness history, clinical status, medication adherence, substance abuse, insight into illness, and violent behavior during the 4 months that preceded hospitalization. Associations between serious violent acts and a range of individual characteristics and problems were analyzed by using multivariable logistic regression. RESULTS: The combination of medication noncompliance and alcohol or substance abuse problems was significantly associated with serious violent acts in the community, after sociodemographic and clinical characteristics were controlled. CONCLUSIONS: Alcohol or other drug abuse problems combined with poor adherence to medication may signal a higher risk of violent behavior among persons with severe mental illness. Reduction of such risk may require carefully targeted community interventions, including integrated mental health and substance abuse treatment.