The effect of glibenclamide and glimepiride, two orally active antidiabetic sulphonylurea derivatives, was investigated on the development of reperfusion-induced arrhythmias and it was compared to their blood glucose lowering action. Arrhythmias were produced by reperfusion following 6 min coronary artery ligation in anaesthetised rats. Glimepiride pretreatment (0.001-0.01-0.1-5.0 mg/kg i.p., 30 min before coronary occlusion) significantly decreased the incidence of irreversible ventricular fibrillation and increased the survival rate during reperfusion (64%, 61%, 60%, and 67% vs. 27% in controls). Glibenclamide produced similar effect (81% survival) only in a dose of 5 mg/kg, while smaller doses were ineffective. The minimal hypoglycaemic dose and the dose required to inhibit significantly the oral glucose loading-induced hyperglycaemia were similar (1 and 0.1 mg/kg, respectively) after glibenclamide and glimepiride. It is concluded that although the blood glucose lowering potency of glibenclamide and glimepiride is rather similar, glimepiride appears to be more potent than glibenclamide in preventing reperfusion-induced cardiac arrhythmias.