Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease.