1. Injury is known to be associated with variable degrees of tissue insensitivity to insulin. We measured insulin resistance in a group of non-obese, glucose-tolerant patients undergoing major elective surgery with an uncomplicated post-operative course. 2. Shortly after surgery, hyperglycaemia (7.3 +/- 0.6 versus 4.2 +/- 0.3 mmol/l glucose pre-surgery, mean +/- SEM, P less than 0.01) with normal insulin concentrations (73 +/- 15 versus 64 +/- 18 pmol/l) suggested the presence of insulin resistance. Counter-regulatory hormones were raised, whole-body protein oxidation was doubled (P less than 0.01) and energy expenditure was up by 18% (P less than 0.01). 3. Insulin sensitivity was quantified by clamping plasma glucose concentrations at 5.6 mmol/l during 24 h of total parenteral nutrition (15% protein, 55% glucose and 30% fat, supplying 1.25 times the measured resting energy expenditure) with a variable infusion of exogenous insulin. After surgery, eight times more insulin was needed than before surgery (14.14 +/- 1.15 versus 1.78 +/- 0.29 pmol min-1 kg-1, P less than 0.001) to maintain euglycemia. 4. After surgery, stimulation of net carbohydrate oxidation (18.8 +/- 1.4 versus 17.2 +/- 1.8 mumol min-1 kg-1 preoperatively, not significant), suppression of lipolysis and lipid oxidation and inhibition of ketogenesis occurred to the same extent as before surgery. Of the infused nutrients, the glucose was all oxidized, amino acids replaced endogenous protein losses (= neutral nitrogen balance) and lipids were stored. Insulin administration caused no further increment in oxygen consumption or energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)