Whereas the lipolytic and diabetogenic consequences of sustained growth hormone (GH) exposure are well described, the metabolic effects of a short-lived physiological GH pulse have only recently been reported. To assess the possible dose-response of such short-term bolus administration of GH, six healthy, male subjects were each studied thrice for 4 1/2 hours after an intravenous (IV) bolus of either 70, 140, or 350 micrograms GH, resulting in peak GH concentrations of 10, 15, and 34 micrograms/L. Observed results include: (1) Time- (but not dose-) dependent changes (P less than .05) in plasma glucose and an acute (from 10 minutes onward), persistent, 40% decrease in forearm glucose uptake. Total glucose turnover decreased steadily with time on all occasions. (2) Time- and dose-dependent increases (P less than .05) in the concentrations of circulating lipid intermediates, with an increase of 3-hydroxybutyrate (3-OHB) from a basal of 35 mumol/L to peak values of 108 +/- 34 (70 micrograms), 176 +/- 46 (140 micrograms), and 232 +/- 51 mumol/L (350 micrograms), forearm uptake of 3-OHB changed in parallel. (3) Respiratory exchange ratio decreased (P less than .05) with increasing GH doses (indicating increased lipid and decreased glucose oxidation), and energy expenditure remained unaffected. (4) Concentrations of insulin, C-peptide, and glucagon were unchanged throughout all studies. We conclude that the stimulating effects of a modest GH bolus on circulating lipid intermediates and lipid oxidation are dose-dependent. This finding underlines the potential role of GH as a principal physiological regulator of fuel consumption in the maintenance of metabolic homeostasis.