The current literature on sex differences in schizophrenia with regard to structural brain abnormalities is inconsistent. Several studies have suggested that male and female patients may differ in severity of brain abnormalities. Efforts to explore this issue have been hindered by small study groups, unbalanced groups (i.e., those with many more men than women), or both. The relatively smaller number of female schizophrenic patients in most studies may have made it more difficult to detect differences between patients and comparison subjects. This study was designed to evaluate brain morphology in a carefully selected group of patients with schizophrenia and healthy comparison subjects who were balanced by sex. Eighty patients (40 male and 40 female) and 80 healthy volunteers matched by sex and age were studied. Magnetic resonance imaging scans were analyzed with the use of an automated method that yields volumes of major brain regions. There was a significant sex-by-diagnosis interaction for ventricular volume, with male patients having significantly larger ventricles than male comparison subjects but female patients showing no significant enlargement in comparison with healthy female subjects. Although the overall distribution of structural brain differences was very similar in the male and female patients, the male patients had a greater number of significant abnormalities than the female patients. These findings indicate that male and female patients with schizophrenia have the same pattern of structural brain abnormalities, but male patients appear to manifest greater severity, especially with regard to ventricular enlargement.