Insulin-like growth factor-I (IGF-I) is a potent protein-anabolic hormone with a glucose-lowering effect and is therefore a possible agent for treating catabolic patients. In this study we investigated the effect of recombinant human (rh) IGF-I on the interorgan flux of glucose under hypo- and normoglycemic conditions in catabolic, anaesthetized, and catheterized dogs. We administered a primed (40 micrograms/kg) continuous (1.5 micrograms.kg-1.min-1) infusion of rhIGF-I (Kabi Biopharma, Stockholm, Sweden) for 180 min together with either a saline (0.9% NaCl) or an amino acid solution (2.2 mg AA.kg-1.min-1 solution of Vamin, Kabi Nutrition, Stockholm, Sweden). RhIGF-I administration lowered plasma glucose levels for approximately 50% of the baseline (P < 0.001) and stimulated glucose uptake from skeletal muscle about twofold (P < 0.01), but did not modify glucose balances across the gut and liver. The same effects were found when infusing rhIGF-I together with AA. A co-infusion of rhIGF-I and glucose to maintain normoglycemic conditions stimulated glucose uptake from skeletal muscle by about fivefold (P < 0.001) and glucose uptake across the gut by about 50%, but reduced the hepatic glucose liberation (-65%; P < 0.01). The rhIGF-I infusion did not alter arterial lactate levels, but stimulated lactate release from skeletal muscle (P < 0.05) and lactate uptake across the liver (P < 0.05). We conclude that rhIGF-I reduces plasma glucose levels mainly by stimulating glucose uptake across skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)