The glutamine conjugation of phenylacetic acid has been investigated in three phenylketonuric and three normal subjects. Both groups of subjects eliminated an oral dose (80 mg) of [14C]phenylacetic acid in the urine almost entirely as phenacetylglutamine. By an isotope dilution technique it was shown that the phenylketonurics excreted on average 5.5 mmoles phenacetylglutamine/g creatinine compared to a value of 1.1 and 0.8 for two normal subjects. It is concluded that the glutamine conjugation mechanism is not defective in phenylketonuria and that it is able to cope with the large amounts of phenylacetic acid produced in this disorder.