The purpose of this study was to determine whether endogenous opioids are involved in the control of skeletal muscle blood flow during locomotory exercise in rats. The radiolabeled miscrosphere technique was used to measure total and regional muscle blood flow. We first determined whether methionine enkephalin (1,000 μ g-kg-1I.V.) would produce vasodilation in muscle vascular beds. We found that methionine enkephalin produced a 36 mm Hg (range of 20-50 mm Hg) drop in mean arterial pressure (Pa), which was associated with decreases in calculated skeletal muscle vascular resistance in anesthetized rats, and that these effects on arterial pressure and skeletal muscle vascular resistance were blocked by the infusion of naloxone (10 μ g-kg-1). Measurements were then made at 5 min of treadmill exercise at 15 m-min-1(0 degree incline) and following exercise in both saline-treated (controls) and naloxone (10 μ g-kg-1)- treated conscious rats. There were no differences between the heart rates, blood pressures, or total muscle blood flows of the two groups. There were also no significant differences between the blood flows to 32 hind limb muscle samples composed of various muscle fiber types. Since naloxone blockade did not affect total or regional muscle blood flow during low intensity exercise, it appears that the endogenous opioids are not required for the normal exercise hyperemia of skeletal muscles