The corpus callosum (CC) has been of interest in schizophrenia research because of its possible role in reduced lateralization and because of its sexually dimorphic characteristics. The literature has been replete with structural brain studies that have yielded equivocal results because of failure to address sex differences, handedness, and overall reductions in total brain volume (TBV) associated with schizophrenia. We performed midsagittal corpus callosum area MRI measurements on 71 chronically ill patients with schizophrenia (52 males, 19 females) and 67 controls (49 males, 18 females) using a semiautomated analytic technique subdividing the corpus callosum into five segments. Consistent with a meta-analysis [J. Neurol., Neurosurg. Psychiatry 58 (1995) 457], reductions in total CC area (after controlling for TBV and age) were found in schizophrenia patients relative to controls. However, our effect size, though not statistically significant, was −0.33 compared to −0.18 for the meta-analysis, indicating greater reductions in total CC area in our group of patients. Statistical significance was achieved only in male patients versus male controls (effect size=−0.50). The effect size remained the same when only right-handers were included in the analysis; thus, handedness did not account for this result. CC size was not related to psychiatric symptoms nor cognitive functioning in this group of patients.