Action potential duration in human and guinea-pig ventricular myocardium is reduced by diltiazem greater than or equal to 10 mumol/l. A reduction of action potential amplitude and maximum upstroke velocity is observed only at high concentrations of diltiazem (30 mumol/l). In depolarized myocardium (rabbit SA- and AV-node, guinea-pig papillary muscle depolarized by (K+)0 = 27 mmol/l) diltiazem greater than or equal to 0.3 mumol/l reduces amplitude and maximum upstroke velocity of the calcium-dependent action potentials. The decrease in maximum upstroke velocity of the slow response in depolarized guinea-pig papillary muscle is enhanced by elevation of the stimulation frequency, as are the negative inotropic effects (use-dependence). In contrast to nifedipine diltiazem also delays the recovery of the maximum upstroke velocity of the slow response after stimulus-induced inactivation. The reduction of maximum upstroke velocity induced by nifedipine is independent of the rate of activation whereas the blockade induced by diltiazem consists of a small blockade during rest and a profound use-dependent blockade.