Abstract Recent studies of the brain using magnetic resonance imaging (MRI) have suggested progressive structural changes in schizophrenics. However, those studies were conducted over periods of less than 5 years and thus lacked sufficient capacity to determine the course and nature of this process. In this study, MRI scans were obtained in 15 schizophrenics and 12 controls at baseline and after 4- and 10-year follow ups. Volumes of the lateral ventricles were measured. Patients were assessed by the Brief Psychiatric Rating Scale (BPRS) at the same two time points: at baseline and at 10-year follow up. After 10 years, a significant lateral ventricular enlargement was found in patients (mean percentage change: +22.9%) but not in controls (5.1%). Although our results are not in disagreement with the neurodevelopmental hypothesis, they do provide strong evidence that in schizophrenia progressive brain reduction occurs even in its chronic stage.