OBJECTIVE: The objective of this work was to assess the reliability and validity of the Medical Outcomes Study Short-Form 12-Item Health Survey (SF-12) in a large sample of people with severe mental illness (SMI). METHODS: We examined the internal factor structure of the SF-12, compared component scores for this sample with normative levels, examined test-retest reliability, and examined convergent and divergent validity by comparing SF-12 scores to other indexes of physical and mental health. RESULTS: The SF-12 distinguished this sample of people with SMI from the general population, was stable over a 1-week interval, consisted of 2 fairly distinct factors, and was related to physical and mental health indexes in expected ways. CONCLUSIONS: The SF-12 appears to be a psychometrically sound instrument for measuring health-related quality of life for people with SMI.