Carcinine was biosynthesized by Carcinus maenas from [14C]beta-alanine, [14C] histidine and [14C] histamine. Since carnosine (beta-alanyl-histidine) could not be detected in crab tissues, biosynthesis of carcinine could only be effected by direct coupling of beta-alanine and histamine resulting from histidine decarboxylation. Biosynthesis of carcinine was weak when [14C]beta-alanine and [14C] histidine were used as precursors. On the contrary when [14C] histamine was used, synthesis was important. Thus carcinine appears to be a product of histamine catabolism. After injecting [14C] histamine, radioactive carcinine was concentrated mainly in the heart and nervous system; nonmetabolized [14C] histamine was recovered mainly in the latter. The nervous system might therefore be the seat of carcinine biosynthesis and thus the site of action of histamine.