Experiments were conducted in normal human volunteers to compare the response of the forearm and calf vessels to contralateral isometric exercise, mental stress, resisted breathing, coughing, and the Valsalva maneuver. Blood flows were measured by means of strain-gauge plethysmography, arterial blood pressure by auscultation, and heart rate by electrocardiography. Isometric exercise of one forearm (at one-third maximal voluntary contraction) for 90 seconds caused an increase in blood pressure and heart rate; the vascular resistance decreased in the resting forearm, and increased in the calf. The decrease in forearm resistance was greater with the subjects supine and attenuated with the subjects standing or reclining head-down. With arterial occlusion of the exercising forearm just prior to cessation of the handgrip, the blood pressure and the calf resistance remained elevated, while the heart rate returned to control. The forearm resistance increased during the occlusion period and remained elevated throughout it. Mental stress caused an increase in heart rate and blood pressure and a dilation of the forearm but not of the calf vessels; these changes were smaller in standing than in supine subjects. Resisted breathing and coughing caused an increase in heart rate and in forearm blood flow, but not in calf blood flow. The Valsalva maneuver was followed by decreases in blood flow to the upper and lower limbs. The different responses in forearm and calf vessels can be explained by a central component which triggers a vasodilator pathway (possibly cholinergic) which is distributed to forearm but not to calf vessels.