WOLFE, R. R. Does exercise stimulate protein breakdown in humans?: isotopic approaches to the problem. Med. Sci. Sports Exerc., Vol. 19, No. 5 (Supplement), pp. S172–S178, 1987. Protein metabolism in exercise has been investigated for 100 yr, yet it is still unclear if exercise induces an increased rate of protein breakdown. We have recently addressed this general question in a series of experiments in human subjects using stable isotopic tracers. In this paper, the results of those studies are reviewed. We have found that in light exercise the de-carboxylation of leucine is increased. However, urea production is not increased correspondingly, nor is the rate of incorporation into urea of nitrogen from either leucine or lysine. Further complicating the picture is the fact that lysine de-carboxylation is not markedly elevated in exercise. From these studies, we must conclude that isotopic techniques which have achieved general acceptance in other circumstances cannot reliably be used to answer the question of whether exercise stimulates protein breakdown in humans. However, these methods do provide results which enable a better understanding of the metabolism of the individual amino acids in exercise.