Insulin production rate has been estimated in healthy male volunteers (n = 16), and evaluated with respect to splanchnic glucose exchange. Insulin production rate was calculated from splanchnic immunoreactive C-peptide output. C-peptide secretion was estimated by the hepatic venous catheter technique both in the basal state and for 2h following ingestion of various glucose loads (0, 12.5, 25, 50, 75, and 100 g). The results demonstrate a basal insulin production rate of 0.017±0.002 U/min (mean±SEM) or 2.04 U/2 h. Values rose in a dose dependent manner from 2.6±1.1 U/2 h after ingestion of 12.5 g of glucose to 10.8±1.1 U/2 h following a glucose load of 100 g. Insulin retention by the liver was estimated at 0.012±0.001 U/min in the basal state, and ranged from 47–85% (70±2%) of production following an oral glucose load. It was also demonstrated 1) that the relative splanchnic glucose output was inversely related to the amount of ingested glucose, and reached a minimum when glucose in excess of 50 g was ingested; and 2) that hepatic glucose retention was directly proportional to insulin production rate (r=0.83; p<0.001; n= 15). It is suggested that the adaptive capacity of the splanchnic bed to retain glucose depending on the amount of ingested glucose guarantees that splanchnic glucose output fluctuates in healthy man only within a narrow range.