Eighteen patients with left hemispheric strokes were compared to 11 patients with traumatic brain injury for frequency and severity of depression, using several mood scales. More than 60% of the stroke patients had clinically significant depressions as compared with about 20% of the trauma patients, even though the two groups had comparable impairments in their activities of daily living and global cognitive functions. Analyses of brain CT scans revealed that the two groups had similar-sized lesions, but the areas of ischemic injury were more anterior than the traumatic lesions. When the results were controlled for lesion location, there were no significant differences in mood between the two groups. The severity of depression was directly correlated with the closeness of the lesion to the frontal pole. These results suggest that depression following left hemispheric brain injury may not be a nonspecific neurological or psychological response, but rather may be a symptom of injury to specific pathways, such as the catecholamine-containing ones, as they pass through the frontal cortex.