Arterio-venous differences across forearm muscle in man in both prolonged starvation and in the postabsorptive state, show an uptake of glutamate and a relatively greater production of glutamine. Splanchnic arteriovenous differences in the postabsorptive state show a net uptake of glutamine and lesser rate of glutamate production. These data suggest that muscle is a major site of glutamine synthesis in man, and that the splanchnic bed is a site of its removal. The relative roles of liver and other tissues in the splanchnic circuit were not directly assessed, only the net balance. These data in man are in conflict with most previous studies in other species attributing the major proportion of glutamine production to the liver and, pari passu, to the splanchnic bed.