The purpose of this study was to develop a method which would produce immediate and sustained lowering of plasma free tryptophan. Glucose, insulin, and mixtures of the two in different concentrations were infused into dogs over a period of 6 hr. Blood was sampled during the course of the infusion for assay of plasma free and total tryptophan, free fatty acids, glucose, and insulin. The infusate found to produce the most significant and sustained reduction in plasma free tryptophan in normal dogs was a mixture of 25% glucose and insulin. The lowering ranged from 26 to 47% during the course of the infusion. When the same infusion mixture was administered to dogs with established portacaval shunts, and elevated plasma free tryptophan concentrations (3.3 +/- 0.3 micrograms/ml compared to normal dogs which had 1.9 +/- 0.1 micrograms/ml), there was a 35% reduction to normal levels (2.0-2.2 micrograms/ml). A glucose-insulin mixture has, therefore, been found which, upon infusion into dogs, significantly lowers plasma free tryptophan levels. The effect of such an infusion on the plasma levels of free tryptophan, and the clinical course of patients with hepatic encephalopathy remains to be determined.