In tryptophan-niacin metabolism, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC 4.1.1.45] is known to play an important role by catalyzing the decarboxylation of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde, a metabolite of tryptophan which cyclizes spontaneously to form quinolinate. In this study, we investigated the effect of either dietary protein or amino acids on the activity of ACMSD in rats. When rats were fed on a high-protein diet ad libitum for several days, their liver ACMSD activity was greatly increased. Kidney ACMSD activity was also slightly elevated by a high-protein diet. Tryptophan, a precursor of the substrate of ACMSD, was not responsible for the increase of ACMSD activity caused by high-protein diet. On the contrary, insufficiency of dietary tryptophan rather elevated ACMSD activity. The increased amount of amino acids other than tryptophan in the diet resulted in the elevation of liver and kidney ACMSD activities. Although the increase of essential amino acids in the diet slightly elevated the liver ACMSD activity, the enzyme activity was enhanced markedly by feeding the diet containing both essential and nonessential amino acids in high concentrations. These results indicate that at least several amino acids, including some essential and nonessential ones, are responsible for the elevation of ACMSD activity which is induced by high-protein diet. Since liver ACMSD activity in adrenalectomized rats was also increased by feeding a high-protein diet, adrenocortical hormone was thought to be unnecessary for such enzyme induction.