Prolonged administration of nitroglycerin and its derivatives results in pharmacodynamic tolerance: although the dosage of these drugs is kept at the same level, their therapeutic effects decrease in amplitude. Experimental and clinical studies have shown that this escape phenomenon is due to depletion of cysteine in the vascular wall. This amino acid, which gives off SH radicals, is indispensable to the ultimate transformation of nitroglycerin enabling in to exert its vasodilator action. Molsidomine does not require any transformation to act on the vascular smooth muscle and should therefore remain insensitive to tolerance. The experimental and clinical data available at present seem to confirm that the effects of molsidomine administered for long periods in the treatment of coronary disease and heart failure are sustained. However, for the long-term effectiveness of molsidomine and nitrites to be compared objectively a prospective double-blind randomized trial would be needed, with both treatments being in optimal doses and intervals of administration.