The occurrence, properties and functions of GTP-cyclohydrolases in mammalian and non-mammalian systems is reviewed. GTP-cyclohydrolases catalyse the removal of C-8 atom from GTP as formic acid. GTP-cyclohydrolase I (EC 3.5.4.16) converts GTP into D-erythro-7, 8-dihydroneopterin triphosphate, whereas GTP-cyclohydrolase II forms 2,5-diamino-4-oxo-6-(5'-phosphoribosyl) -amino pyrimidine, a possible intermediate in the biosynthesis of riboflavin. GTP-cyclohydrolase I is the first enzyme in the biosynthesis of tetrahydrobiopterin, a cofactor of the monooxygenases of the aromatic amino acids. It is the rate limiting enzyme in many mammals, but not in man. Recently, patients with GTP -cyclohydrolase I deficiency were described, a variant form of tetrahydrobiopterin-deficient hyperphenylalaninaemia.