We determined the effect of exhaustive exercise on the acid-base balance, O2 consumption, and cardiac output in dogs and pigs to examine which species was comparable with humans in its physiological response to exercise. We ran 11 dogs and 11 pigs on a motor-driven treadmill at steady-state (heart rate 75% maximum) and exhaustive (maximum heart rate) exercise levels. Measuring heart rate, cardiac output, and aortic pressure via implanted probes we obtained arterial and venous blood samples before, during, and after exercise to determine hematocrit, blood gas tensions, pH, and lactic acid levels. Dogs had a twofold greater work capacity than the pigs, but the dogs could not run at maximal heart rate as long as the pigs did. Although O2 consumption correlated well with cardiac output and total work in both species, dogs were capable of a greater range of values. The acid-base studies showed that exhaustive exercise in the pigs resulted in a severe metabolic acidosis, whereas this did not occur in dogs. Respiratory alkalosis was noted in dogs. This suggested that the supply of O2 to the working muscles of the pig was insufficient to maintain aerobic metabolism. The pigs' responses to exercise conformed to those found by others in the human, suggesting that the pig is a more appropriate model for some exercise studies.