Hindlimb and total blood flow and O2 uptake were measured in anesthetized paralyzed dogs in which venous outflow from the left hindlimb (less paw) was directed through the femoral vein. After ventilation on room air, 10 dogs were given 3 mg/kg phenoxybenzamine + 10 ml/kg dextran and 10 other dogs were isovolemically exchanged with 10 ml/kg dextran without alpha-block while continuing to be ventilated on room air. All animals were then ventilated with 9.1% O2 in N2, followed by a recovery period on room air. Total and limb peripheral resistances were lowered by alpha-block, but total and limb blood flow changed little from control levels. Both total and limb O2 uptake were decreased below control values during hypoxia. Cardiac output and limb blood flow increased during hypoxia in both groups. Although alpha-block caused O2 extraction by the whole body to be less during hypoxia than in unblocked dogs, the hindlimb in both groups extracted O2 equally well. We concluded that skeletal muscle was not overperfused relative to O2 demand when alpha-blocked during hypoxia.