We report behavioral and cognitive characteristics of 12 patients with caudate nuclei lesions, 11 unilateral and one bilateral. These patients developed an acute behavioral change characterized by apathy, disinhibition, or a major affective disturbance. The pattern of personality change correlated with size and location of lesion within the caudate but not the laterality. Seven patients were further compared with matched controls on a series of neuropsychological tests. Their performance was impaired on tasks requiring planning and sequencing. They had short attention spans and decreased free recall of episodic and semantic items with good recognition memory scores. Similar behavioral and cognitive changes also occur in early Huntington's disease, frontal-lesioned patients, and caudate-lesioned animals, and correspond to disturbances of specific frontal-caudate circuits. These results implicate the caudate nuclei in mediating prefrontal behaviors and possibly in the conceptual integration of memories.