The pattern of brain asymmetries was visualized on computed tomography (CT) scan in patients with a single acute cerebrovascular lesion. Patients were divided into those with typical or reversed frontal and/or occipital asymmetries. Among patients with a typical occipital asymmetry, those with left frontal or left basal ganglia lesions showed a significantly higher frequency of major depression and significantly higher depression scores than patients with similar lesion location but with reversed occipital asymmetry or those with a typical asymmetry and lesions in other (left or right) brain areas. Among patients with a reversed occipital asymmetry, there was no significant association between left frontal or left basal ganglia lesions and depression. This study demonstrates that the previously reported significant association between post-stroke major depression and lesion location is restricted to patients with a typical occipital asymmetry and is not present in patients with a reversed occipital asymmetry.