Magnetic resonance imaging (MRI) and positron emission tomography (PET) with fluorodeoxyglucose were used to study the size and shape of the corpus callosum in 20 patients with unipolar depressive disorder and 16 normal controls. An automated algorithm outlined the corpus callosum and divided it into quarters. The anterior and posterior quarters of the corpus callosum were larger in depressed patients than in controls, findings similar to most earlier MRI studies of the corpus callosum in schizophrenics. The patient-normal difference was more marked in females than in males. PET glucose metabolic values were higher in patients with thinner or smaller callosums. The presence of marked sex differences makes future larger studies controlling body size and age important.