1. The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2. Propafenone, 10(-7) -5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (ICa) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak ICa at +10 mV was 5 x 10(-6) M. 3. The voltage-dependence of ICa inactivation was shifted in the hyperpolarizing direction in the presence of 5 x 10(-6) M propafenone. 4. A frequency-dependent relative block by propafenone was observed after repetitive depolarizing test pulses at a frequency of 0.5 and 1 Hz. The recovery of ICa from inactivation was prolonged by propafenone and the reactivation exhibited an additional exponential component attributed to the slow release from drug block of Ca channels. 5. These results suggest that propafenone, at therapeutic concentrations exhibits Ca channel blocking properties that may be involved in its antiarrhythmic mechanism.