This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first-admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups.