The metabolic effects of recombinant human insulin-like growth factor-I (IGF-I) were assessed in five groups of normal male overnight-fasted volunteers receiving infusions of either 0, 5, 7.5, 15, or 30 micrograms/kg.h IGF-I during 8 h, resulting in total plasma IGF-I concentrations 127 +/- 7, 247 +/- 30, 389 +/- 39, 573 +/- 62, 620 +/- 105 ng/ml, respectively. Glucose consumption (euglycemic glucose clamp) increased dose dependently during IGF-I infusion (P < 0.001) up to 6.7 +/- 1.3 mg/kg. min in the 30 micrograms/kg.h group. Plasma triglyceride concentrations decreased with increasing doses of IGF-I (P < 0.03); the fall was 43% in the 30 micrograms/kg.h group. Plasma free fatty acid concentrations decreased during 7.5, 15, and 30 micrograms/kg.h IGF-I by 23%, 34%, and 48%, respectively. IGF-I lowered plasma beta-hydroxybutyrate concentrations in a dose-dependent manner (P < 0.025). Plasma concentrations of leucine and alpha-ketoisocaproate decreased dose dependently (P < 0.001 and P < 0.015). Whole body leucine flux (1-13C-leucine infusion technique) decreased with increasing doses of IGF-I by 41% during 30 micrograms/kg.h, indicating decreased whole body protein breakdown. Leucine oxidation into 13CO2 decreased with increasing doses of IGF-I (P < 0.045) by 57% in the 30 micrograms/kg.h group, suggesting inhibition of irreversible loss of leucine. Plasma C-peptide and insulin concentrations decreased dose dependently (P < 0.005 and P < 0.02), indicating diminished insulin secretion. Thus, acute elevation of plasma IGF-I concentrations in man results in metabolic effects which are qualitatively similar to those described previously of insulin.