Insulin-like growth factor I (IGF-I) has been found to increase insulin sensitivity and suppress insulin secretion, thereby having a potential interest as a therapeutic agent for non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to investigate the direct actions of IGF-I (400 ng/ml) on human pancreatic islets, or on rat pancreatic islets, during a 48 h period in tissue culture. Insulin-like growth factor I did not affect medium insulin accumulation, DNA or insulin content or short-term glucose-induced insulin release of human islets. However, in rat islets the peptide induced a significant decrease in the insulin increase ratio in response to 16.7 mmol/l glucose. In conclusion, the present data suggest that IGF-I does not directly affect the function of human pancreatic beta-cells. If this in vitro data can be extrapolated to the in vivo situation, it suggests that the observed inhibitory effects of IGF-I on serum insulin levels may be secondary to peripheral effects of the peptide.