MRI and post-mortem studies indicate an increased prevalence of cavum septi pellucidi (CSP) in schizophrenia and affective disorder. The aim of this study was to characterize the CSP and the septal tissue among patients with schizophrenia, patients with affective disorder, and control subjects. The volumes of CSP and septal tissue were measured in post-mortem brains in 42 patients with schizophrenia, 14 patients with affective disorder, and 17 normal control cases by planimetry of serial sections. Enlargements of CSP (>100 mm(3)) were found in eight of the 42 (19%) patients with schizophrenia. There were no significant differences in CSP volumes between patients with affective disorder and controls. Enlarged CSP in schizophrenia were not associated with reduced septal tissue volumes. By contrast, a significant positive correlation between volumes of CSP and septal tissue volumes in patients with schizophrenia (P = 0.03) and in control cases (P < 0.01) was found, but not in patients with affective disorder (P = 0.53). The finding of enlarged CSP in schizophrenia strongly supports the hypothesis of an early developmental abnormality in this key structure of the limbic system.