Rats made phenylketonuric by a diet containing high levels of either phenylalanine alone, or phenylalanine and tyrosine, show a marked reduction in total cerebral stores of serotonin. Evidence from studies both in vitro and in vivo indicates that an important mechanism of this impairment in the metabolism of serotonin is the inhibition by high levels of these amino acids of the active transport of the precursor of serotonin, 5-hydroxytryptophan, into brain.