Postoperative hypoalbuminemia occurs frequently; however, the cause of this disorder is not clear. In a double-blind, placebo-controlled study we investigated to what extent hypoalbuminemia and protein catabolism are caused by counterregulatory stress hormones, which play an important role in the metabolic changes that follow surgery. We simulated the postoperative endocrine response in healthy volunteers with a cocktail of the counterregulatory hormones epinephrine, glucagon, and hydrocortisone. Saline was infused as a control in a second experiment. Serum albumin and stress hormone concentrations and nitrogen balance were measured for 34 h and were compared with published values for patients after abdominal surgery. Triple-hormone infusion mimicked the endocrine response after abdominal surgery adequately. It caused a negative nitrogen balance comparable with that after moderately severe surgery but no hypoalbuminemia (serum albumin < 35 g/L), although serum albumin was slightly reduced relative to the control group. No net nitrogen loss or hypoalbuminemia occurred after saline infusion. In conclusion, counterregulatory stress hormones do not cause hypoalbuminemia in healthy volunteers, but do produce protein catabolism.