Elevated plasma concentrations of growth hormone impair glucose tolerance and insulin sensitivity of peripheral tissues. To study the effect of short-term exposure to growth hormone concentrations elevated into the upper physiologic range (7-10 ng/ml) on splanchnic carbohydrate metabolism, both splanchnic glucose output (SGO) and substrate exchange after ingestion of a 75-g glucose load were determined by means of the liver vein catheter technique in six healthy volunteers after growth hormone administration. Growth hormone was infused at a rate of 2 micrograms/kg X h starting 120 min before and continuing for 150 min following the glucose load. Control studies without growth hormone administration were performed in seven subjects. SGO was 104 +/- 10 (SEM) mg/min in the postabsorptive state and increased to 43.4 +/- 2.2 g during the 150-min period following glucose ingestion. Growth hormone infusion did not alter basal SGO (130 +/- 14 mg/min), nor the splanchnic exchange of lactate, pyruvate, and free fatty acids, whereas basal production of beta-OH-butyrate was increased twofold; following glucose ingestion a higher proportion of the given glucose load escaped the splanchnic bed after growth hormone exposure (66.9 +/- 6.8 g/150 min; P less than 0.005). The insulin production rate (basal 14 +/- 2 mU/min; following oral glucose 7.0 +/- 0.8 U/150 min) as calculated from C-peptide release from the splanchnic area was unaltered by growth hormone exposure in the basal state (14 +/- 3 mU/min), but augmented after glucose ingestion (14.8 +/- 1.5 U/150 min).(ABSTRACT TRUNCATED AT 250 WORDS)