To elucidate the short-term actions of growth hormone on insulin sensitivity and forearm metabolism, we have studied six normal male subjects receiving a 6-h hyperinsulinaemic euglycemic clamp with and without a concomitant 4-h growth hormone infusion. When infused, serum growth hormone rose to 25 +/- 4 mU/l and during administration of insulin serum insulin increased by 11 +/- 1 mU/l. During euglycemic clamp, administration of growth hormone decreased forearm glucose uptake after 180 min and onward (240 min 0.216 +/- 0.031 vs 0.530 +/- 0.090 mg/100 ml/min, p less than 0.05). Glucose infusion rate (240 min 2.83 +/- 0.24 vs 4.35 +/- 0.28 mg.kg-1.min-1, p less than 0.05) and glucose disposal rate (240 min 3.57 +/- 0.17 vs 4.00 +/- 0.15 mg.kg-1.min-1, p less than 0.05) also decreased. Growth hormone persistently increased hepatic glucose production after 120 min. After 210 min, all circulating lipid intermediates increased slightly. The decrease in forearm glucose uptake and glucose infusion rate and the increase in hepatic glucose production was observed before there was any detectable increase in circulating levels and forearm uptake of lipid intermediates. These data suggest that growth hormone induces insensitivity to insulin in liver, muscle and fat after 120, 180 and 210 min respectively. The early effects of growth hormone on glucose metabolism seems independent of changes in the rate of lipolysis.