Regional and total blood flow and O2 uptake (VO2) were measured in 10 anesthetized paralyzed dogs in which venous outflow from the left hindlimb (less paw) was directed through the femoral vein. After being ventilated on room air during a 40-min control period, they were ventilated on 12.0% O2 for 40 min, 9.2% O2 for 40 min, and again on room air for 40 min. A second group of 10 was treated the same after they were given 1.0 mg/kg propranolol to block beta-adrenergic receptors. Neither limb blood flow nor cardiac output changed significantly during moderate hypoxia in either group; both increased in severe hypoxia but only in the no-beta-block group. Limb VO2 was not decreased significantly in either group during moderate hypoxia but total VO2 was decreased in the beta-block group. Total VO2 was decreased in both groups during severe hypoxia but limb VO2 was maintained in the beta-block group. beta-Block prevented the fall in total and limb peripheral resistance seen in severe hypoxia but did not alter the consistently more efficient utilization of total O2 delivery shown by the limb in comparison to the whole body by higher O2 extraction ratios and lower venous O2 pressure. beta-Vasodilator receptors evidently played an active part in the vasodilatation seen during severe hypoxia.