All previously studied antiarrhythmic drugs which also have local anaesthetic properties reduce the maximum rate of depolarization (MRD) of cardiac muscle. Recent evidence suggested that lidocaine and diphenylhydantoin (DPH) might have a different mode of action, because they did not reduce MRD except at high concentration. The latter evidence, however, was obtained from tissues nourished by solutions containing 2.7-3 mM potassium. In the present experiments, the effects of lidocaine and DPH were studied in solutions with 5.6 and 3 mM KCl. In the former, both drugs reduced MRD at concentrations similar to those found in the blood of treated patients, but in low [KCl] higher concentrations were necessary. It was concluded that there was no reason to suppose that the mode of action of lidocaine and DPH on the cardiac membrane is fundamentally different from that of quinidine, procaine, procainamide and other compounds which interfere directly with depolarization.