In a recent study, it was demonstrated that following i.v. injection of glucose, plasma insulin levels increased more in cholestatic rats than in control rats. This could theoretically be due to either a potentiated insulin secretion or an inhibited liver extraction of insulin in cholestatic rats. In the present study, we report the influence of obstructive jaundice on insulin secretion from isolated islets of Langerhans 3 weeks after bile duct occlusion or sham operation in rats. We found that insulin secretion from islets of control rats (250 +/- 29 microU/ml) and of bile duct-occluded rats (260 +/- 24 microU/ml) was not significantly different in a medium with a low glucose concentration (3.3 mM). In contrast, at a high glucose level (16.7 mM), an increased insulin secretion was seen from islets of cholestatic rats (469 +/- 14 microU/ml) as compared with control rats (370 +/- 19 microU/ml) (p less than 0.001). These results indicate that the increased plasma insulin levels found in vivo during cholestasis may not merely reflect a decreased liver clearance but be attributed to a potentiation of glucose-induced insulin secretion.