The effects of the new calcium blocker (CAB), bepridil hydrochloride (BP), on calcium influx and isometric tension development resulting from activation of both the potential-dependent (60 mM KCl) and the receptor-operated (10 microM norepinephrine) calcium channel were studied in rings of rabbit thoracic aorta. BP was compared to nifedipine (NF), verapamil hydrochloride (VP) and diltiazem hydrochloride (DZ). The effects of the CABs were compared to those of alpha-1 adrenergic receptor blocker, prazosin (0.01, 0.1 and 10.0 microM), and to those of the inorganic nonspecific calcium channel blocker, lanthanum chloride (0.1, 1.0 and 5.0 mM). All organic CABs tested between 0.1 and 10.0 microM significantly inhibited potential-dependent activity with respect to both calcium influx and development of isometric tension (NF greater than BP = VP greater than DZ). However, only BP additionally inhibited both aspects of receptor-operated activity in a concentration-dependent fashion. In an isolated guinea-pig Langendorff heart preparation, all CABs increased coronary flow (NF greater than DZ greater than BP = VP) and reduced cardiac contractile force (VP = NF greater than DZ greater than BP) without significantly altering spontaneous rate. In the absence of extracellular calcium ion (0 calcium solution + 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid), norepinephrine caused a phasic contractile response in rabbit thoracic aorta which was suppressed by VP and NF but not by DZ or BP. These results suggest that the four calcium blockers have differential effects on calcium channel activity and on intracellular calcium release in vascular smooth muscle.