Two of the nonsedating antihistaminic drugs, terfenadine and astemizole, have recently been recognized in rare cases to induce the syndrome of torsades de pointes, i.e. QT interval prolongation and life-threatening ventricular tachycardia. Each was found to prolong cardiac repolarization when its metabolic elimination was impaired, such as by liver disease or drugs that inhibit the 3A family of cytochrome P450. In vitro studies indicate that this action is due to blockade of one or more of the cardiac potassium channels that determine the duration of the action potential. Prescription guidelines are now available to reduce the risk of developing arrhythmias with these two drugs. Two agents recently marketed in the United States, Ioratidine and cetirizine, appear to lack the ability to prolong repolarization and induce torsades de pointes. Evaluation of the potential cardiac actions of investigational antihistamines is essential and may be of value for some of the older conventional agents.