This investigation was designed to examine the interactive effects of blood flow (Q) and oxygen delivery (QO2) on peak oxygen consumption (VO2peak) and fatigue in the gastrocnemius-plantaris dog muscle in situ. Arterial oxygen content (CaO2) was manipulated by varying the fraction of inspired O2 to create a high- and a low-QO2 treatment at each of three levels of Q (approximately/=800, 1100 and 1500 ml x kg(-1) x min(-1)). Isometric contraction was achieved by stimulation with one tetanic contraction per second (200 ms at 70 Hz) at supramaximal voltage for 10 min to achieve VO2peak under each condition. Arterial and venous blood were sampled, and Q and tension development (TD) were measured at 1, 5 and 10 min into the contractions. Fatigue was calculated as the percentage (%) change in TD from min 1 to min 10. While VO2peak was highly correlated to QO2 (R = 0.97) in both the moderate- and high-Q conditions, both low-Q conditions had a significantly (P < 0.05) higher VO2peak than predicted by the QO2-VO2 relationship. In addition, VO2 peak was significantly greater in the low-Q versus the high-Q condition. Fatigue (% decrease in TD) was significantly different between the two low-Q conditions [Low-QO2=38.4 (6.9); Norm QO2=27.9 (1.8)] and the two moderate-Q conditions [low-QO2=31.1 (7.3); high-QO2 = 20.9 (4.1)] but not between the two high-Q conditions [normal-QO2 = 10.4 (6.9); high-QO2 = 11.9 (4.5)]. In the two conditions of equal QO2, fatigue was significantly less in the high-Q condition (10.4%) compared to the low (27.9%). Thus, it seems that there is a unique interaction between Q and QO2 which determine the VO2peak and rate of fatigue in contracting muscle.