The effects of the 5-hydroxytryptamine2 (5-HT2) antagonists ketanserin and ritanserin on ischaemia- and reperfusion-induced arrhythmias were investigated in pentobarbitone-anaesthetised rats. Both ketanserin (3 mg kg-1) and ritanserin (1 mg kg-1) significantly reduced the incidence of ventricular fibrillation (from 60 to 25% and 88 to 12%, respectively) and the mortality induced by reperfusion after 5 min of myocardial ischaemia. Neither drug significantly altered the number of ventricular ectopic beats, the incidence of ventricular tachycardia, ventricular fibrillation, or mortality during the first 25 min of coronary artery occlusion. Significant dose-dependent reductions in heart rate and arterial blood pressure were observed with all doses of ketanserin (0.1-3 mg kg-1) and ritanserin (0.3 and 1 mg kg-1), but neither drug had any major effect on arterial blood gases or pH. In isolated guinea pig and rat atria and ventricular muscle preparations, ketanserin (10(-5) M) and ritanserin (3 X 10(-5) M) reduced the maximal driving frequency, whereas 5-HT itself was without effect. The results suggest that the antiarrhythmic activity of ketanserin and ritanserin observed in this study was probably not due to 5-HT2 receptor or alpha 1-adrenoceptor blockade, but may have been due to a direct action on cardiac muscle.