Review of the clinical characteristics and neuroanatomy of 20 reported cases of alien hand syndrome (AHS) and a patient of our own confirm that AHS is actually two distinct syndromes. Frontal AHS occurs in the dominant hand; is associated with reflexive grasping, groping, and compulsive manipulation of tools; and results from damage to the supplementary motor area, anterior cingulate gyrus, and medial prefrontal cortex of the dominant hemisphere and anterior corpus callosum. Callosal AHS is characterized primarily by intermanual conflict and requires only an anterior callosal lesion. the occurrence of frontal AHS in the dominant limb can be explained by an increased tendency for dominant limb exploratory reflexes coupled with release from an asymmetrically distributed, predominant nondominant-hemisphere inhibition. Callosal AHS is best explained by hemispheric disconnection manifested during behaviors requiring dominant-hemisphere control.