The membrane site of action and intracellular effects of diltiazem on heart and blood vessels are briefly discussed and compared to those of other calcium entry blockers, mainly verapamil and nifedipine. Diltiazem seems to have another site of action in the membrane than verapamil and nifedipine. Even if its main action is exerted at the cell membrane level, diltiazem may, at high concentrations, appears to have intracellular effects. Similar to the haemodynamic effects of verapamil and nifedipine, those of diltiazem are determined not only by direct actions on heart and peripheral vessels, but also by sympathetic reflex activity which modulates the direct effects. Two aspects of the myocardial protective action of diltiazem are discussed, the ability of the drug to reduce the frequency of ventricular dysrhythmias associated with ischaemic damage, and the ability to protect the ischaemic myocardium during reperfusion.