Neuropathological, obstetrical, and epidemiological evidence increasingly suggest that some cases of adult-onset schizophrenia have prenatal or neonatal etiological roots. We evaluated the developmental histories of 23 monozygotic twin pairs discordant for schizophrenia to determine when they markedly and permanently began diverging from each other in motor skills or unusual behavior. Seven of the twins (30%) who later developed schizophrenia had become permanently different from their cotwins by age 5 years. The early divergence group differed from the others by multivariate tests (p = 0.002) for within-twin pair effects and by univariate tests for physical anomaly scores (p = 0.01), total finger ridge counts (p = 0.001), family history of psychosis (p = 0.004), and serious perinatal complications or low birth weight (p = 0.05). It is concluded that some cases of adult-onset schizophrenia are associated with prenatal events, which may include neurodevelopmental abnormalities or specific insults such as anoxia or infectious agents.