The metabolism of phenylalanine and tyrosine was evaluated in six normal men, five chronically uremic men, and three men undergoing maintenance hemodialysis. Phenylalanine, tyrosine, and 13 acidic metabolites of those amino acids were measured in plasma postabsorptively and in plasma and urine after a phenylalanine load of 100 mg/kg. In addition, five normal subjects and five dialysis patients ingested L-[14C]-phenylalanine (uniformly labeled) with the load. In uremic and dialysis patients, plasma phenylalanine rose higher and fell more gradually after the load, and tyrosine rose more slowly. The 24-hr urinary concentrations of phenylalanine and tyrosine were similar in the three groups. At 24 hr, cumulative expiration of 14CO2 was 20.2% in the dialysis patients and 28.4% in the normal subjects. Plasma phenylalanine levels and 14CO2 expiration varied with protein intake in normal subjects. In uremic and dialysis patients, plasma phenyllactic acid, p-hydroxyphenylacetic acid, and p-hydroxybenzoic acid were elevated, the last one markedly so. Moreover, plasma phenylpyruvic acid (PPA) and mandelic acid were detected only in dialysis patients. After the phenylalanine load, plasma conjugated phenylacetic acid rose in uremic patients, and PPA increased transiently in some dialysis patients. In urine of dialysis patients, concentrations of benzoic acid and conjugated o-hydroxyphenylacetic acid were decreased, and PPA was sometimes increased. The data suggest a mild impairment in the hydroxylation of phenylalanine which does not result in marked changes in plasma or in urinary metabolites after a phenylalanine load.