Muscle metabolism in man was studied by measuring the arterial and deepvenous concentrations of glucose, lactate, pyruvate, free fatty acids, beta-hydroxybutyrate and aceacetoacetate, and forearm blood flow. After the subjects had fasted overnight, their arterial free fatty acid and ketone levels rose continuously during a period of 90 min, leading to increased ketone body uptake by muscle. Hence, for each subject, a relation was obtained between arterial concentrations and arterial-deepvenous differences of beta-hydroxybutyrate and acetoacetate. As the ketone body utilization increased, the release of lactate rose as well. In spite of these alterations the uptake of glucose remained unchanged. These findings underline the current notion that accelerated ketone uptake reduces pyruvate oxidation but not glucose uptake by muscle.