We assessed the plasma amino acids, glucose, and insulin responses of obese and lean control subjects to midafternoon carbohydrate snacks. After a standard 400 kcal lunch, eight lean and nine obese subjects received, at 2PM, a 30 g sucrose snack; blood samples were obtained at hourly intervals until 6 PM. Each subject participated in four similar studies in which the carbohydrate snack was consumed alone or with 250, 500, or 1,000 mg of L-tryptophan (Trp), offered as a capsule. The obese group exhibited elevated plasma levels of the branched-chain amino acids, phenylalanine and tyrosine, and the levels of these amino acids declined much less in response to carbohydrate intake than in lean controls. As a consequence, the plasma ratio of Trp:large neutral amino acids (Trp/LNAA ratio), which normally rises after carbohydrate consumption, showed virtually no change in the obese group. The plasma Trp/LNAA response of this group did not reach control values even when carbohydrate intake was increased to 50 or 75 g. Peak plasma Trp concentrations and Trp/LNAA ratios after 250, 500, and 1,000 mg Trp doses were also significantly lower in the obese. Since brain Trp uptake is strongly correlated with the plasma Trp/LNAA ratio, which in turn determines the rate of brain serotonin synthesis, the blunted Trp/LNAA response to carbohydrate intake in the obese could contribute to alterations in the serotonin-mediated regulation of food intake.