The calcium channel-inhibiting drugs diltiazem, verapamil and nitrendipine represent three general classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents (ICa++) in rabbit sternomastoid muscle fibers was examined. ICa++ were recorded at room temperature using a vaseline gap voltage clamp. ICa++ measured had similar kinetics to those reported in rat skeletal muscle, were partially blocked by 0.5 mM CdCI2 and could be reduced by substitution of Mg++ for Ca++. Diltiazem reversibly blocked ICa++ in a concentration-dependent manner with the 50% inhibitory concentration (IC50) being 63 microM. Verapamil was slightly more potent with approximately 50% block of ICa++ occurring at 10 microM. In contrast, nitrendipine at concentrations from 1 to 10 microM had no blocking action on ICa++, even after 20 min of exposure. Thus, although Ca++ channels in mammalian skeletal muscle fibers are readily blocked by cadmium, diltiazem and verapamil, these channels appear to be insensitive to the dihydropyridine compound nitrendipine.