The effects of the portein and amino acid composition in the diet on the biosynthesis of protein-bound lipoic acid (the active form of lipoic acid for oxidative decarboxylation of [alpha]-keto acids, such as pyruvic acid and [alpha]-ketoglutaric acid) were observed. Decreased incorporation of lipoic acid into the total mitochondrial protein of rat liver was revealed in the low protein group. The incorporation of the acid/mg N of liver mitochondria of the low protein group was unexpectedly higher than that in the standard diet group. In the lysine-, tryptophan- or threonine-deficient group, the incorporation of lipoic acid into the mitochondrial proteins was decreased, but in the methionine- or phenylalanine-deficient group, almost the same incorporation was observed as the standard diet group.