In the conscious, chronically instrumented dog, leucine-enkephalin ([Leu5]ENK), 35 micrograms/kg injected intravenously, increased heart rate, respiratory rate, systolic and diastolic systemic arterial pressures, mean pulmonary arterial pressure, and cardiac output. After pentobarbital-induced anesthesia, the same dose of [Leu5]ENK decreased heart rate, systemic and pulmonary arterial pressures, and cardiac output. Responses both before and after pentobarbital were blocked by naloxone. These results indicate that barbiturate anesthesia can reverse the cardiovascular stimulatory activity of intravenously administered [Leu5]ENK.