When intravenous access cannot be obtained in an emergency, the endotracheal route of emergency drug administration can be used for epinephrine, atropine, and lidocaine. Optimal drug dosages for endotracheal administration as well as the amount and type of diluent are presently unknown. We compared central intravenous, peripheral intravenous, intraosseous, and intratracheal administration of epinephrine 1:10,000 in both normotensive and hemorrhagic shock dogs. The shock model consisted of 50% blood volume depletion over 15 min. Epinephrine was administered in a dose of 0.01 mg/kg (0.1 cc/kg) by the intraosseous route, central, and peripheral intravenous routes followed by a 5 cc normal saline flush. Intratracheal administration consisted of epinephrine 0.01 and 0.02 mg/kg diluted 1:1 and 1:2 with normal saline or sterile water and administered deep into the tracheo-bronchial tree using a 30-cm catheter. The effect of epinephrine was assessed by the response of the arterial blood pressure. Epinephrine was equally effective by the intraosseous, central intravenous, and peripheral intravenous routes in terms of time to onset of action, time to peak effect, and magnitude of effect on systolic, diastolic, and mean arterial pressures in both the shock and non-shock animals. The duration of effect was significantly longer (P less than 0.02) for the intraosseous route of administration. The endotracheal route of administration was unreliable and not reproducible in either the normotensive or shock animals. In 8/12 episodes in normotensive animals, including 5 trials with double doses of 0.02 mg/kg and dilutions of 1:1 and 1:2, and in 4/9 studies with shock animals including three with double doses, there was no discernable response of systolic or diastolic blood pressure.