To determine the effect of the 75 g oral glucose tolerance test on carbohydrate and lipid metabolism, the splanchnic exchange of glucose, lactate, pyruvate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate as well as the release of insulin, C-peptide, glucagon and pancreatic polypeptide were evaluated in eight healthy male volunteers in the basal state and for 150 min following glucose ingestion. Oral glucose loading was followed by a rapid rise in splanchnic output of glucose (mean +/- SEM; 154 +/- 12 mmol/150 min), pyruvate (1.2 +/- 1.2 mmol/150 min) and lactate (8.6 +/- 2.0 mmol/150 min), whereas there were reductions in the splanchnic uptake of non-esterified fatty acids (-10.7 +/- 4.4 mmol/150 min) and the splanchnic output of beta-hydroxybutyrate (-4.8 +/- 3.3 mmol/150 min) and acetoacetate (-3.0 +/- 1.2 mmol/150 min). In parallel, splanchnic output of insulin (12.3 +/- 2.7 nmol/150 min), C-peptide (36.1 +/- 5.0 nmol/150 min) and transiently of pancreatic polypeptide rose, whereas that of glucagon fell (-0.58 +/- 0.21 nmol/150 min). Even at 150 min after glucose ingestion, splanchnic output and arterial concentrations of glucose, lactate, insulin and C-peptide were still above their respective basal values while those of non-esterified fatty acids and glucagon were reduced. Taking into account the partial suppression of endogenous glucose production by ingested glucose it is concluded that, in normal postabsortive man, only 49-63% of a 75 g oral glucose load is retained by the splanchnic bed during the first 150 min, the rest being available for non-hepatic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)