L-Amino acids, when administered intra-peritoneally either individually or as mixtures to fasted rats, blocked the epinephrine-induced hyperglycemic response. The injection of 2.5 mmoles/kg of either arginine, lysine, leucine, isoleucine, threonine, or tryptophan inhibited epinephrine-induced hyperglycemia 76–89%. The same dosage of methionine or valine had less effect on the hyperglycemic response (42 and 32% respectively). By contrast phenylalanine and histidine did not exhibit significant inhibitory actions (4 and 6% respectively) at the same dosages. Equivalent amounts of bovine serum albumin, casein hydrolysate, or a mixture of 10 essential amino acids were no more inhibitory than either valine or methionine alone. In addition the non-metabolizable amino acids, α-aminoisobutyric acid and 1-aminocyclo-pentanecarboxylic acid are about as potent as methionine and valine in blocking epinephrine hyperglycemia. Several metabolites of tryptophan, namely indole-3-acetic acid, quinolinic acid, and hydroxyanthranilic acid blocked epinephrine hyperglycemia 87–99%. Xanthurenic acid, kynurenic acid, and serotonin inhibit the response 48–65%. DL-Kynurenine was the least potent exhibiting a 24-percent inhibition. In addition the tryptophan analogue, DL-α-methyltryptophan produced an 47-percent inhibition. The fact that no correlation could be found between the capacities of the amino acids to produce hypoglycemia and their capacity to inhibit epinephrine-induced hyperglycemia suggests than insulin is not involved in preventing the hyperglycemic response. This idea is supported by the observation that tryptophan inhibits epinephrine-induced hyperglycemia to the same extent in both intact and diabetic rats.