The infusion of recombinant insulin-like growth factor I (IGF-I) causes a decrease in plasma glucose and insulin. In this study we examined whether or not IGF-I directly affects islet hormone release by means of a rat pancreas perfusion system. A superphysiologic concentration of IGF-I (2 nM) elicited a slight but significant decrease in insulin release under the perfusate glucose concentration of 120 mg/dl. A pharmacological concentration of IGF-I (200 nM) significantly suppressed the increase in insulin release in response to an increase in the perfusate glucose concentration (from 4.5 mM to 12.8 mM), but did not affect the decrease in insulin release in response to a decrease in the perfusate glucose concentration (from 6.9 mM to 2.8 mM). Glucagon release was not influenced by IGF-I in these experiments. These results suggest that IGF-I potentially inhibits the insulin release from islet B-cells directly, but its pathophysiological significance may be slight considering its partial inhibition at superphysiologic concentrations and its stable plasma level.