To test the hypothesis that hyperinsulinism is responsible for reduced branched-chain amino acids in cirrhotics, plasma amino acids were sequentially determined in 8 controls and 8 matched cirrhotics during continuous i.v. insulin infusion. An artificial endocrine pancreas which infused glucose was used to sustain euglycemia. Basal plasma insulin levels were high and branched-chain amino acids were reduced in cirrhotics. Insulin infusion raised insulin levels to 3 to 4 times basal values. During the test, the decline in branched-chain amino acids was markedly higher in controls who had similar steady-state insulin levels. Not only did the level of branched-chain amino acids in controls reach the values seen in cirrhotics after 60 min, but the levels continued to fall at a significantly higher rate throughout the second hour. Glucose consumption and the ratio of glucose infused/steady-state insulin—a measure of tissue sensitivity to insulin—were markedly reduced in cirrhotics and positively correlated with the decline in branched-chain amino acids. In cirrhotics, insulin effects on carbohydrate and branched-chain amino acid metabolism were reduced. Low branched-chain amino acid levels in cirrhotics are not likely to depend only on hyperinsulinism.