Patients with single stroke lesions, verified by computerized tomography, involving either cortical tissue or restricted entirely to subcortical structures were examined for mood disorders. Those with left anterior lesions, either cortical or subcortical, had significantly greater frequency and severity of depression than patients with any other lesion location. A strong correlation between the severity of depression and proximity of the lesion to the frontal pole was observed for both left cortical and subcortical groups. Right hemisphere lesions did not show the same correlation with depression but were associated with a significantly higher incidence of undue cheerfulness. These findings demonstrate the importance of the location of subcortical lesions in poststroke mood disorders and suggest that anterior subcortical structures may play an important but lateralized role in the production or regulation of mood.