Because of the well-recognized age-related changes in peripheral tissue sensitivity to insulin and the demonstrated impact of insulin on blood amino acid profiles in young individuals, we evaluated the influence of insulin level and age on the concentration of tryptophan and its ratio to the sum of the large neutral amino acids (LNAA). The ratio of the plasma concentrations of tryptophan and the LNAA (leucine, isoleucine, valine, tyrosine, and phenylalanine), may be an important determinant of the rate at which tissues synthesize neurotransmitters, such as catecholamines and serotonin. Each of five healthy young (21 to 34 yr) and five healthy old subjects (67 to 85 yr) received, on separate occasions, euglycemic insulin infusions at rates of 6, 10, 30, and 400 mU × m-2 × min-1. Basal plasma tryptophan concentrations and LNAA levels were similar in young and old. Both tryptophan and LNAA levels decreased in an insulin dose-dependent manner (P < .02). The dose-response effect of insulin on tryptophan levels in the elderly was less than in the young (P < .03), while the response of the LNAA was similar in both age groups. The ratio of tryptophan to LNAA was less in the old when compared to the young (P < .03) but increased in the two age groups in an insulin-dose-dependent fashion (P < .02). Maximal plasma tryptophan decrements were 39% and 32%, and maximal LNAA declines were 58% and 61% in young and old, respectively, during the 400 mU × m-2 × min-1 studies. The impact of the changes in tryptophan and LNAA levels with relative preservation of their ratio on neurotransmitter synthesis and central nervous system function are discussed.