These experiments were designed to determine: 1) if lactate can be extracted from the arterial blood and utilized by resting skeletal muscle of the dog, and 2) if lactate uptake or production by skeletal muscle is influenced by the level of circulating free fatty acids. Skeletal muscle arteriovenous differences in lactate were measured at several arterial lactate and free fatty acid concentrations. With sodium pentobarbital anesthesia and a low concentration of free fatty acids, arterial lactate concentrations of 1-2 mM were associated with extraction of lactate; however, when circulating free fatty acids were elevated (greater than 1 mM), no extraction of lactate occurred at these lactate concentrations. The relationship between arterial free fatty acids and uptake or release of lactate demonstrated in these in vivo studies suggest that the inhibition of free fatty acid release from adipose tissue that occurs when the arterial lactate concentration increases may function facilitate the metabolism of lactate by skeletal muscle.