A new experimental model of hyperphenylalaninemia was proposed. Combination of p.chlorophenylalanine, strongly inhibitor of phenylalanine hydroxylase, and cotrimoxazole, presumably inhibitor of dihydropteridine reductase, produced a good inhibition of phenylalanine hydroxylation in vivo. Thus phenylalaninemia reached values similar to those found in PKU patients, without administration of excess phenylalanine. Tyrosine concentrations remained near the control values and a phenylketonuria occurred.