The ability of tetrodotoxin and verapamil to block Ca++-dependent action potentials (CaP) produced in superfused, canine cardiac Purkinje fibers was studied using intracellular microelectrodes. CaP were produced in fibers superfused with a Na+-free (substituted by tetraethylammonium chloride) high Ca++ (16.2 mM) Tyrode’s solution (pH 7.4 or pH 6.0). In 30 fibers studied two populations of resting membrane potentials (RMP) were observed. In one, the mean RMP was –43 ± (SE) 3 mV, in the second it was -63 ± 2 mV. The high RMP was seen at pH 7.4, while the low RMP was observed at pH 6.0. It was possible to block low pH, CaP with verapamil alone, while high RMP, high pH, CaP could be totally blocked only with a combination of verapamil plus tetrodotoxin.