OBJECTIVE The antiarrhythmic efficacy of adenosine during states of AV-nodal reentrant tachycardias is well known and clinically established. Adenosine is also able to reduce ventricular arrhythmias when applied before coronary ligation in rats. Hypoxia or ischemia leads to an increased production of adenosine by cardiac myocytes. The purpose of this study was to evaluate if adenosine also has a direct antiarrhythmic effect on ischemia-induced ventricular fibrillation. METHODS In this study, the antiarrhythmic effects of adenosine on ventricular fibrillation during global (low flow) ischemia were evaluated in isolated guinea pig hearts perfused by the method of Langendorff. RESULTS Adenosine showed a dose-dependent prolongation of the peak to peak interval of the ventricular ECG signal during ventricular fibrillation until ventricular flutter or tachycardia occurred at a concentration of 2 mmol/L. At a concentration of 20 mmol/L, adenosine converted ventricular fibrillation into ventricular tachycardia with intermittent periods of asystole. This conversion of ventricular fibrillation to asystole was antagonised by 200 micromol/L theophylline. CONCLUSIONS Adenosine appears to have an antiarrhythmogenic effect both in supraventricular and ventricular rhythm disturbances. During myocardial infarction, where huge amounts of adenosine are present in ischemic regions, asystole may respond to adenosine antagonists.