SUMMARYTo clarify the influence of blood flow with high-oxygen (02)-affinity blood on oxygen consumption (VO ) in submaximally exercising skeletal muscle, we perfused the isolated dog gracilis (n = 8) contracting under 1 Hz stimulation alternately with normal and high-02-affinity blood, with a constant arterial 02 content (Ca 0 ) and varying perfusion rates. The average P50 (oxygen partial pressure (PO ) for half-saturation at pH 740, P20 of 40 mmHg at 37°C) of the high-02-affinity blood prepared by carbamylation was 15 5 mmHg, and that of the normal blood 33 7 mmHg. With normal blood perfusion, the average VO above 6 ml min-' (100 g)-1 of 02 delivery (Ca 0o x flow) was 4 38 ml min-1 (100 g)-' (range 4 17-468 ml min-1 (100 g)-1), and JVO at the 02-delivery range of 6-5 and 4-2 5 ml min-1 (100 g)-1 decreased to 3 96 and 243 ml min-(100 g)-1, respectively. The PO of venous effluent (Po02) at the 02 delivery of 6 ml min-' (100 g)-1 was 33 mmHg. With low-P,0 blood perfusion, V was significantly less 0o2 than with normal blood, both below the 02 delivery level of 6 ml min-m (100 g)-1 and above it, even in the fairly high 02 delivery range of 8 5-12 ml min-1 (100 g)-1 (P < 0 05). Thus, high blood flow did not compensate for the reduced VO caused by high-02-affinity blood. At values of P°2less than 33 mmHg, VO with low-P,0 blood was not significantly different from that with of ,02 50 ws0o2sg normal blood (P > 0 05). The reduced VO2 in submaximally exercising skeletal muscle might be due to a slower 02 dissociation from the high-02-affinity red cells and to a limited 02 diffusion resulting from the lower P' 02 value (which reflects mean end-capillary P02).