Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus reduce the frequency of opening of these channels in response to depolarization. The result is a marked decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, is cardio selective, nifedipine is vascular smooth muscle selective, while diltiazem exhibits intermediate selectivity. Methods: In the present study, the effect of two Ca++ channel blocker, Verapamil and Diltiazem were compared on the isolated frog heart by using adrenaline & calcium chloride as standard on frog heart contractility. Results and conclusion: Adrenaline and calcium chloride increased the amplitude of contraction of isolated perfused frog heart. The L- type of Ca2+ channel blockers verapamil and diltiazem produced dose dependent (2g, 4g, 8g, and 16g) reduction in the amplitude of contraction produced by calcium chloride in isolated perfused frog heart. There was no statistical significant difference (p > 0.05) between the inhibitory effect of diltiazem and verapamil on calcium chloride induced contraction of isolated frog heart.