The metabolism of phenylalanine-C14 was studied in three different groups of rats: normal animals, phenylalanine-deficient animals and rats which had been maintained on a high (5 and 7%) phenylalanine diet from 21 days of age and considered to be "experimentally phenylketonuric". In normal rats the injection of DL-phenylalanine-1-C14 resulted in the excretion of more radioactivity in the CO2 and urine than did the injection of DL-phenylalanine-3-C14. However, the radioactivity in the proteins was higher after the injection of DL-phenylalanine-3-C 14. Para-fluorophenylalanine-3-C14, an analogue of phenylalanine, produced higher levels of radioactivity in the CO2 and urine than did DL-phenylalanine-3-C14. This analogue was incorporated into the proteins in significant quantities and was also rapidly transformed into tyrosine-C14. The tyrosine-C14 was then incorporated into the proteins. A second phenylalanine analogue, beta-2-thienylalanine-3-C14 produced only trace quantities of radioactive C14O2 but highly radioactive urine. In all of the organs, except the pancreas, this analogue was only incorporated into the proteins in trace amounts. After the addition of either non-radioactive parafluorophenylalanine or beta-2-thienylalanine to the injected phenylalanine-C14, there was, in general, an increase in the ratio of tyrosine-C14/phenylalanine-C 14 incorporated into protein. More radioactive CO2 and urine were produced, and the radioactivity of the protein was decreased. Both of these effects were most pronounced when a third analogue, 2-amino-3-phenylbutanoic acid, was used. This compound was also incorporated into the proteins. After treatment with a low-phenylalanine diet the radioactive CO 2 and urine produced when phenylalanine-3-C14 was injected indicated that there was a general reduction in the rate of phenylalanine metabolism. The level of incorporation of radioactivity in the proteins of the phenylalanine-deficient rats varied little from normal values. More phenylalanine than tyrosine was incorporated into protein. When attempts were made to induce an experimental phenylketonuria it was found that if the rats were placed on the high phenylalanine diet too early, the phenylalanine was toxic. Injection of phenylalanine-C14 into phenylketonuric rats resulted in an increase in the release of the radioactivity in the CO2 and urine and a decrease in the radioactivity of the proteins compared to the results obtained in normal rats. The ratio of tyrosine-C14/phenylalanine-C14 incorporated into proteins in these phenylketonuric rats was also lower. DL-tryptophan-3-C14 was also injected into phenylketonuric rats. The only difference from the values obtained for normal rats was a slight elevation of the radioactive content of the urine in the phenylketonuric rats.