L-tryptophan was found to consistently inhibit in vivo growth of the Walker 256 intramuscular carcinoma in rats. Doses of 8, 4 and 2 mM/kg body weight of L-tryptophan inhibited the tumor approximately 55%, 50% and 35%, respectively, the inhibitions being statistically significant. Other L-amino acids such as histidine, proline, leucine and glutamic acid, given in identical fashion and dosage as L-tryptophan, showed no inhibitory effect; L-phenylalanine showed only a very weak inhibitory effect at borderline levels of statistical significance. It was concluded that the action of L-tryptophan was specific and not related to an ‘amino acid imbalance’ brought about the administration of simply any amino acid in large dosages. The primary mechanism of action of L-tryptophan was thought to be due to its inhibition of the enzyme PEP carboxykinase, resulting in a block to gluconeogenesis and retardation of cancer cachexia. The toxicity of L-tryptophan was found to be nil in dosages below 6 mM/kg animal body weight/day and only slight at double that dosage. Morbidity, characterized by anorexia, was present at a dosage range of 8–12 mM/kg/day but disappeared within 24–36 h after the drug was stopped. In some experiments L-tryptophan administration resulted in a lower net animal weight gain than in control animals, whereas histidine, proline, leucine and/or glutamic acid administration stimulated the net animal weight gain; the latter effect was thought to represent at least in part a correction of cachexia, rather than simply a compensation for lack of nutrient intake by tumor bearing