Several anatomic abnormalities in the brains of schizophrenics have frequently been reported. However, it remains unresolved whether such neuropathology is fully expressed and static at the onset of psychosis or whether further deterioration evolves during the course of illness. To address this important question, we obtained serial volumetric magnetic resonance images (MRI) of the cerebral ventricles of 18 patients with schizophrenic symptoms. Repeated blind measurements of total ventricular volume (TVV) revealed < 2% error of the segmentation method. Over a 2-3 year period, the rate of ventricular expansion (RVE) was 2.2 +/- 1.6 cm3/year in the patients and 0.7 +/- 0.6 cm3/year in controls. The RVE in the patients was not normally distributed, but clustered into two groups: a group similar to controls (n = 10; RVE, 0.9 +/- 0.5 cm3/year) and a group with a significantly greater rate of expansion (n = 8; RVE, 3.9 +/- 0.7 cm3/year) (P < 0.001). These results suggest that there are at least two subpopulations within the schizophrenias: one with relatively static ventricles and another with progressively enlarging ventricles. At least two distinct etiologic processes may thus underlie the clinical presentation of schizophrenic symptoms. Factors which might influence ventricular expansion (neuroleptic compliance, alcohol and recreational drug abuse, and some clinical correlates) could not account for differences between groups.