The acute response to a continuous infusion of somatostatin (0.1-0.15 micrograms/kg min) for between 30 to 180 min in five burn patients was investigated. In all patients the somatostatin reduced both insulin and glucagon levels, and the glucagon was reduced to a greater extent (on a molar basis) than the insulin. In all cases, the rate of production of glucose measured by the primed-constant infusion of 6,6-D2-glucose was suppressed during the infusion. Plasma glucose concentration, however, did not change in a predictable manner. Glucose clearance was consistently depressed, and the magnitude of change in glucose clearance was directly correlated to the magnitude of the reduction in insulin concentration induced by the somatostatin infusion (P less than 0.01). In one additional study, insulin was infused during the somatostatin infusion in order to maintain the basal level of insulin throughout the infusion, thus creating a selective drop in glucagon concentration. In this case, glucose clearance did not fall and the plasma glucose concentration declined owing to the lower rate of glucose production. These results suggested that in burn patients hyperglucagonemia stimulates glucose production and that insulin is effective in enhancing glucose clearance.