The metabolic and cardiovascular adjustments of the whole body and skeletal muscle were studied during moderate and severe acute anemia. In 15 anesthetized dogs, venous outflow from the gastrocnemius-plantaris muscle group was isolated. Cardiac output (QT) muscle blood flow (QM), total body and muscle oxygen uptake (VO2) were determined during a control period, and at 30 and 60 min of either (i) moderate anemia (n = 8) in which the mean hematocrit (Hct) was 25% or (ii) progressive anemia (n = 7) in which the mean Hct values were 25% at 30 min and 16% at 60 min of anemia. Muscle VO2, QT, and QM were increased in both groups at 30 min of anemia. By 60 min, QT and QM declined to preanemic control values in the moderate anemia group; whole body VO2 was maintained at the control level. Arterial oxygen transport was the same in the two groups at both 30 and 60 min of anemia despite the difference in Hct at 60 min. Muscle VO2 showed a further and similar rise in both groups between 30 and 60 min of anemia. These data show that the rise in muscle VO2 during acute anemia was not directly proportional to the degree of the hematocrit reduction. Further, the findings suggest that the muscle VO2 response was related to the decrease in arterial oxygen transport.