Tryptophan oxidation was evaluated in 6 institutionalized phenylketonuric subjects (age range 5–13 years) by measuring the urinary excretion of oxidation metabolites following administration of L-tryptophan loads by mouth. Observations were made when subjects were on a general diet, a low-phenylalanine diet and a low-phenylalanine diet containing added L-phenylalanine. At some time during each dietary regime, the subjects also received tryptophan by mouth, 100 mg/kg body weight. Measurement was made in urine of: 1. 3-hydroxykynurenine; 2. kynurenine; 3. acetyl kynurenine; 4.3-hydroxyanthranilic acid; 5. xanthurenic acid; 6. kynurenic acid; 7. anthranilic acid; 8.3-indole-acetic acid; 9. o-hydroxyphenylacetic acid; and 10. phenylpyruvic acid. Excretion of tryptophan-kynurenine metabolites (products 1–9) amounted to 3.78 μmoles/kg/24 h and was similar to that of control subjects while on all diets. With tryptophan loading on normal diets, excretion of metabolic products was lower than for control subjects. With tryptophan loading on low-phenylalanine diets, the excretion of tryptophan metabolites was 2–3 times higher than the mean value of 22.7 μmoles/kg/ 24 h observed in normal subjects. The response to loading when the diet contained added phenylalanine was variable, since two patients excreted normal amounts of metabolites and three excreted amounts several times greater than the controls. Excretion of indole and 3-indoleacetic acid was abnormally elevated with and without tryptophan loading on normal diets and when phenylalanine was added to the low-phenylalanine diets. Values in μmoles/kg/24 h were: 3-indoleacetic acid 1.7 (normal); 2.5–9.4 (PKU); indican 6.24 (normal); 14.9–24.6 (PKU).