OBJECTIVE: Neuroimaging studies have provided robust evidence that schizophrenia is associated with structural brain abnormalities. However, the underlying pathophysiology of these changes is still unknown. By evaluating brain morphology early in the course of illness, confounding effects of treatment and duration of illness are minimized. The goal of this study was to evaluate brain structure in patients early in the course of schizophrenia who had received no or minimal neuroleptics. METHOD: Magnetic resonance imaging was used to evaluate 12 male and 12 female patients experiencing their first episode of schizophrenia (mean duration of psychotic episode = 14 weeks) and 12 male and 12 female normal volunteers equivalent in age, height, and parents' socioeconomic status. A totally automated method was used to analyze scans, yielding volumes of brain tissue and CSF, divided into lobes. RESULTS: The patient group had significantly more total CSF than the comparison subjects. This was accounted for by higher levels of intersulcal CSF as well as ventricular CSF. There were no differences in total volume of brain tissue between the two groups, but patients had a significant regionally specific decrement in frontal lobe tissue compared with the normal subjects. CONCLUSIONS: These findings indicate that structural brain abnormalities are present very early in schizophrenia and may not be due to factors such as treatment or chronicity of illness. Rather, since the abnormalities are present near the onset of the illness, a neurodevelopmental mechanism may be suggested.