The effects of four sulphonylureas (gliclazide, glibenclamide, chlorpropamide and glipizide) on insulin binding and insulin action were studied in vitro using primary cultured rat hepatocytes. Cells were cultured for 20 h in the absence or presence of the sulphonylurea. The binding of insulin to rat hepatocyte monolayers was not altered in cells previously exposed to gliclazide at 0.7, 7.0 or 70 micrograms/ml; and to glibenclamide, chlorpropamide, or glipizide at 0.1, 1.0 and 10 micrograms/ml. Insulin-induced down regulation was not affected by a simultaneous exposure of hepatocyte monolayers to any of the four agents. The stimulatory effect of insulin on alpha-aminoisobutyric acid uptake by the cells was not modified following exposure to the drugs. These studies indicate that the sulphonylureas tested do not have a direct effect on insulin receptors in hepatocytes; and that, in vitro, they do not alter the post-receptor events involved in the insulin-induced stimulation of amino acid transport in these cells.