The roles of absolute and relative oxygen uptake (VO2 and percent of muscle group specific VO2 max) as determinants of the cardiovascular and ventilatory responses to exercise over a wide range of active muscle mass have not previously been defined. Six healthy men performed four types of dynamic exercise--one-arm curl, one-arm cranking, and one- and two-leg cycling at four different relative work loads--25, 50, 75, and 100% of VO2 max for the corresponding muscle group. VO2 during maximal one-arm curl, one-arm cranking, and one-leg cycling averaged 20, 50, and 75%, respectively, of that for maximal two-leg cycling. Cardiac output was linearly related to VO2 with a similar slope and intercept for each type of exercise. Heart rate at a given %VO2 max was higher with larger active muscle mass. In relation to %VO2 max, systemic resistance was lower and plasma catecholamine levels were higher with larger active muscle mass. The cardiovascular responses to exercise are determined to a large extent by the active muscle mass and the absolute oxygen uptake, with the principal feature appearing to be the tight linkage between systemic oxygen transport and utilization.