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OBJECTIVE: Epidemiologic evidence linking obstetric complications to schizophrenia has been positive but inconclusive. One reason for the lack of conclusive evidence may be the inconsistency in measuring disturbances of fetal/neonatal brain development based on general obstetric markers of maternal health. The authors used data from the National Collaborative Perinatal Project to examine the relationship between schizophrenia and other nonaffective psychoses and a theoretically derived measure of hypoxic-ischemia-related fetal/neonatal complications. METHOD: Six hundred ninety-three men and women (average age 23) born to a community sample of women between 1959 and 1966 were followed up an average of 19 years after early childhood assessments. Subjects with DSM-IV schizophrenia and other nonaffective psychoses were identified using the Diagnostic Interview Schedule and best-estimate consensus diagnoses. RESULTS: Hypoxic-ischemia-related fetal/neonatal complications were associated with a doubling of the risk of developing a psychotic disorder, compared with no relevant complications (6.9% versus 1.4%). When mood disorders were excluded from the group of psychotic diagnoses, the risk of schizophrenia and other nonaffective psychoses associated with hypoxic-ischemia-related fetal/neonatal complications was strikingly elevated, compared with no relevant complications (5.75% versus 0.39%). Nonpsychotic mood disorders were unrelated to these fetal/neonatal complications. Schizophrenia and other nonaffective psychoses were most strongly associated with hypoxic-ischemia-related fetal/neonatal complications of disordered growth and development. CONCLUSIONS: The data show a strikingly elevated, graded, independent risk of schizophrenia and other nonaffective psychoses associated with this classification of antecedent hypoxic-ischemia-related fetal/neonatal complications.