Two patients with chronic unilateral medial frontal lobe lesions, including the supplementary motor area, were given tasks of response preparation and response inhibition. Whereas the patient with a left-sided lesion, like normal controls, did benefit from preparatory information regarding a subsequent response, the patient with a right-sided lesion did not. On a task requiring the inhibition of an inappropriate response, the patient with a left-sided lesion again performed normally. Conversely, the patient with a right-sided lesion had significant problems inhibiting the extremity contralateral to the lesion. We postulate that the medial frontal lobe may participate in response preparation and response inhibition by modulating the levels of excitability of the motor systems. Our findings also suggest that the right hemisphere may have a dominant role in mediating these processes. © 1987, American Medical Association. All rights reserved.