It is unclear whether the neuroanatomical abnormalities associated with schizophrenia change over the course of the disorder. We addressed this issue by examining whether the magnitude of structural brain abnormalities in patients with chronic schizophrenia was related to their duration of illness. Thirty-nine subjects with schizophrenia (34 male, 5 female, range of illness duration 2–31 years) were scanned using magnetic resonance imaging. Images were segmented into grey and white matter, cerebrospinal fluid and dura/blood vessels using the Structural Magnetic Resonance Toolkit (SMaRT). Voxel-based analysis identified brain areas whose volume varied significantly with time since the first onset of psychosis. Right medial temporal, medial cerebellar and bilateral anterior cingulate grey matter volume, and white matter volume in the right posterior limb of the internal capsule, were all negatively correlated with illness duration ( p<0.002). Conversely, illness duration was positively correlated with the volume of the right globus pallidus ( p<0.002). These correlations were not a function of chronological age or age at illness onset. The inverse correlation between right frontal, temporal and cerebellar volumes and the time since the onset of schizophrenia could reflect progressive tissue loss following the first episode of the disorder.