OBJECTIVE: Investigations of the relation of clinical features of schizophrenia to neuroanatomic measures have produced inconclusive results. The purpose of this study was to examine measures of whole- brain volume in men and women and relate them to clinical subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of cranial, brain, and ventricular and sulcal CSF volume were examined in 81 patients with schizophrenia (50 men and 31 women), divided into subgroups based on their symptom profiles, and 81 demographically matched healthy comparison subjects. RESULTS: The men had higher cranial and brain volumes than the women. The patients had smaller cranial and brain volumes than the comparison subjects; they also had higher ventricular CSF volumes and thus higher ventricle-brain ratios (VBRs). Ratio elevations were larger for the female than for the male schizophrenic patients. The patients with predominantly negative symptoms of schizophrenia had higher VBRs and sulcal CSF-brains ratios than the comparison subjects, although the component volumes did not differ. The patients with predominantly Schneiderian symptoms had higher VBRs than the comparison subjects but showed reduced cranial and brain volumes. The paranoid patients had normal VBRs, reduced sulcal CSF-brain ratios, and lower cranial and sulcal CSF volumes. CONCLUSIONS: The results suggest two patterns of neuroanatomic whole- brain abnormalities that differ in severity according to the relative prominence of negative, Schneiderian, and paranoid symptoms. These patterns may reflect differential involvement of dysgenic and atrophic pathophysiological processes. Sex moderates abnormalities in the neuroanatomic features of schizophrenia.