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 2 h 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 less than 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.