Blood flow was studied in dog hind-limb muscle isolated except for femoral and sciatic nerves. At constant perfusion pressure, elevation of aortic pressure produced by blood transfusion or intravenous epinephrine administration elicited a three- to fourfold increase in blood flow in perfused muscle. The blood flow increase evoked by epinephrine could be prevented by maintaining aortic pressure at control levels by means of a pressure compensator. Carotid artery occlusion had little effect on muscle blood flow whereas release of carotid occlusion produced marked increases. Cold or procaine block of the femoral or sciatic nerves resulted in little change in blood flow, whereas nerve section distal to the block produced large transient increases in flow. It is concluded that muscle blood flow increase after aortic pressure elevation is the result of active vasodilation and that increase in muscle blood flow after nerve section is due to stimulation of vasodilator fibers or direct stimulation of vascular smooth muscle by pressure changes produced by the twitch contraction associated with nerve section.