To clarify the role of skeletal muscle in the regulation of plasma amino acid levels, we investigated the response of skeletal muscle to changes in plasma amino acid levels using the perfusion technique of rat hindquarters. The hindquarters of overnight-fasted rats were perfused with a medium containing no amino acids (0 X) and amino acids with plasma levels simulating normal (1 X) or 5 times the normal levels (5 X). Each amino acid level in the perfusate changed in various ways during a 2 h perfusion. The characteristics of amino acid flows in response to the changes in their perfusate levels were divided into four groups as follows: the amino acids which are always taken up irrespective of their plasma levels: glutamate and aspartate; those which are always released: alanine, glutamine and glycine; those which are taken up or released depending on their plasma levels: valine, leucine, isoleucine, serine and (threonine); and those which are released at lower, but neither taken up nor released, at higher plasma levels: tyrosine, phenylalanine, tryptophan, histidine, methionine, asparagine, arginine, lysine and proline. Comparing these results with the data of liver perfusion (Bloxam, D.L. (1971): Br. J. Nutr., 26, 393-422), we assumed that skeletal muscle plays a role complementary to liver in the regulation of plasma amino acid levels.