Use of endotracheal drug therapy during cardiopulmonary resuscitation (CPR) is reviewed. Endotracheal drug therapy--instillation of a drug solution directly into an endotracheal tube for absorption into the circulation via the alveoli--may be used during CPR when venous access is limited. Administration of drugs via a central vein is the most efficient route, but a central i.v. line may not be present and peripheral venous administration may not be possible because of vasoconstriction, trauma, other patient-related factors, or absence of personnel trained to insert i.v. catheters. An endotracheal tube is usually inserted during CPR; in most cases, this procedure can be performed outside the hospital by emergency medical personnel. Basic life-support measures are not interrupted during endotracheal administration as they are in intracardiac drug administration. Drugs that may be administered by the endotracheal route include epinephrine, atropine sulfate, lidocaine hydrochloride, naloxone hydrochloride, and metaraminol bitartrate. Endotracheal delivery of calcium salts, sodium bicarbonate, and bretylium tosylate is not recommended. Pharmacokinetic data for drugs administered endotracheally are lacking; therefore, dosage recommendations are empirical. Usually, the same dose is administered endotracheally as by the i.v. route. Little is known about choice and volume of diluent and the best anatomic site of application. Endotracheal drug administration may replace intracardiac injection as the second-line alternative to intravenous drug injection during CPR.