The metabolic impact of total parenteral nutrition (TPN) was evaluated in nine subjects who underwent esophagogastroplasty for esophageal carcinoma. On the second day after operation all subjects were connected to an artificial endocrine pancreas. In four patients only glucose was infused (5.5 mg/kg X min). The remaining five subjects received glucose (4.0 mg/kg X min), amino acid (0.5 mg/kg X min), and lipid emulsion (0.6 mg/kg X min). Plasma glucose concentration was kept constant over 24 hours. However, both insulin requirement (111 +/- 15 v 70 +/- 2 mU/kg X h) and plasma insulin level (99 +/- 15 v 30 +/- 7 microU/mL; P less than .01) were higher during combined TPN. Blood lactate concentration was higher during glucose infusion (P less than .05). No difference was found in blood concentrations of pyruvate, alanine, and ketone bodies. Both glycerol and FFA were higher during combined TPN. The ratio between glucose infusion rate and the average plasma insulin level was calculated as an index of insulin-mediated glucose metabolism; G/I X 100 was markedly reduced during combined TPN (4.5 +/- 0.8 v 20.7 +/- 3.7; P less than .05). Plasma FFA levels were positively correlated with plasma insulin concentration (r = .76) and inversely correlated to G/I X 100 (r = -.73; both P less than .05). In conclusion, during combined TPN a state of insulin resistance is induced and more insulin is required to achieve a normal glucose utilization.