Since chronic congestive heart failure syndromes are associated with both elevated circulating levels of angiotensin II and potentially lethal ventricular tachyarrhythmias, we investigated the effect of angiotensin II on voltage-dependent cardiac Na+currents. Single-channel Na+currents in neonatal rat ventricular myocytes were studied using the patch clamp method in the cell-attached mode. Angiotensin II applied outside the patch increased the frequency of opening and rates of activation and inactivation of single-channel Na+currents within the patch. These effects were mimicked by the phorbol ester 12 -O-tetradecanoylphorbol-13 -acetate (TPA) and were prevented by prior incubation with TPA. Therefore, we propose that angiotensin II modulates cardiac Na+currents by a cytoplasmic second messenger, perhaps protein kinase C, and this may predispose toward arrhythmia.