Cisapride is used widely for the treatment of diabetic gastroparesis. There is some evidence that cisapride may influence insulin secretion. The aim of this study was to evaluate the effect of cisapride on plasma concentrations of glucose, insulin and C-peptide in response to oral and intravenous glucose loads. Twelve normal subjects took cisapride and placebo, each for 10 days using a randomized, double-blind, crossover design. In each treatment phase, the plasma glucose, insulin and C-peptide response to intravenous (0.5 g/kg) and oral (75 g) glucose loads was evaluated on separate days. Gastric emptying of the oral glucose load was also measured. After the intravenous glucose load, plasma concentrations of C-peptide were higher (P< 0.01) on cisapride when compared with placebo (e.g. peak C-peptide 2.08+/-0.25 nmol/L vs 1.78+/-0.22 nmol/L, P< 0.01) while there was no significant difference in plasma glucose or insulin. Cisapride had no effect on the rate of gastric emptying of the oral glucose load. Mean plasma concentrations of insulin and C-peptide were higher after oral glucose on cisapride than placebo, but these differences were not significantly different. These observations indicate that cisapride may increase glucose-stimulated insulin secretion.