The relevance of the steric configuration to the effects of two non-selective beta-adrenoceptor antagonists without intrinsic sympathomimetic activity (+)- and (--)-bupranolol (10 and 50 micrograms/kg i.v.) and (4)- and (--)-propranolol (100 and 500 micrograms/kg i.v.) on the i.v. glucose tolerance test (IVGTT) were investigated in conscious, normoglycemic dogs. The effects of the beta-adrenoceptor antagonists on plasma glucose, and insulin levels and insulin-glucagon ratio following IVGTT were evaluated by calculating the respective areas under the curve (AUC). The AUC values for plasma glucose were significantly increased by the (--)-configuration of both beta-adrenoceptor increased by the (--)-configuration of both beta-adrenoceptor antagonists. In the (+)-configuration only propranolol (500 micrograms/kg i.v.) increased the AUC value for plasma glucose significantly. The AUC values for plasma insulin and also for the plasma insulin-glucagon ratio were significantly increased by (--)-propranolol (500 micrograms/kg i.v.) and by (--)-bupranolol (10 and 50 micrograms/kg i.v.). Thus the impairment of glucose tolerance, due to suppression of the plasma insulin level, depends mainly on the beta-adrenoceptor antagonistic activity of the (--)-configuration.