To investigate the metabolic basis of skin wound healing, we measured in anesthetized rabbits the responses of protein kinetics in scalded skin to insulin and amino acids. L-[ring-(13)C(6)]Phe was infused on the 7th day after the ear was scalded, and the scalded ear was used as an arteriovenous unit to reflect protein kinetics in skin wound. The ipsilateral carotid artery was clamped to control the wound blood flow within four- to fivefold the normal skin rate to measure the enrichment difference in the scalded ear during hyperaminoacidemia. Neither insulin (2.5 mU x kg(-1) x min(-1)) nor amino acid (2.5 mg x kg(-1) x min(-1)) infusion alone improved net protein balance in the skin wound. In contrast, combined infusion of insulin and amino acids increased the net protein balance in skin wound from -6.5 +/- 4.5 to 1.4 +/- 5.2 micromol x 100 g(-1) x h(-1) (P < 0.01, control vs. insulin plus amino acids). We conclude that there is an interactive effect of insulin and sufficient amino acid supply on protein metabolism in skin wound, meaning that their combined anabolic effect is greater than the sum of their individual effects.