1 The effects of agents which produce membrane stabilization (class I), beta 1-adrenoceptor blockade (class II), prolongation of the cardiac action potential (class III) or inhibition of the slow inward current (class IV) were investigated for their ability to increase the ventricular fibrillation threshold (VFT) or to modify the fall in VFT consequent upon coronary artery ligation in the anaesthetized rat. 2 The class I agent, Org6001, increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 3 The class II agent, metoprolol, failed to increase VFT of normal myocardium but reduced the postligation fall. 4 The class III agent, melperone, increased VFT of both normal and ischaemic myocardium whereas the class IV agent, nifedipine failed to influence VFT in either region. 5 Bepridil (class I and IV) was similar to Org6001 and sotalol (class II and III) in that it increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 6 Measurement of VFT before and after coronary artery ligation in the rat constitutes a rapid and reproducible screen to detect antifibrillatory activity. 7 The results also suggest that in the rat, the low currents used (approximately 400 microA) do not release substantial quantities of catecholamines whereas these may be released by coronary artery ligation.