The effect of chronic angiotensin converting enzyme (ACE) inhibition on the incidence of fatal ventricular fibrillation during regional myocardial ischaemia and reperfusion is not known. A reduction in cardiac angiotensin II and/or a vagomimetic response may result in antiarrhythmic activity. Pigs pre-treated with the ACE inhibitor trandolapril 0.3 mg.kg-1 or placebo orally for 10 days were subjected to thoracotomy. The left anterior descending coronary artery was ligated (CAL) for 20 min and reperfused for 45 min. Trandolapril decreased cardiac ACE activity and prevented the fall in the ventricular fibrillation threshold (VFT) during ischaemia: after 5 min of ischaemia the VFT in the trandolapril group was 25.5 +/- 4.6 mA (mean +/- SEM) vs 13.1 +/- 2.2 mA in the placebo group (P < 0.05). Trandolapril also decreased the incidence of spontaneous ventricular fibrillation during reperfusion to 1/6 vs 6/7 in the placebo group (P < 0.05). Heart rate in the trandolapril group fell. During ischaemia, trandolapril increased blood flow in the non-ischaemic zone, but decreased blood flow in the central ischaemic zone of the left ventricle. Similarly it decreased tissue levels of phosphocreatine in this zone. During reperfusion trandolapril increased blood flow both in non-ischaemic and central ischaemic zones. Chronic oral pre-treatment with trandolapril resulted in marked antifibrillatory effects which were associated with inhibition of cardiac ACE activity and a decreased heart rate.