Endogenous opioid peptides such as Met-enkephalin have diverse physiological actions, which include hypotension and bradycardia in anesthetized animals. The exact sites, the mechanism and the physiological significance of the cardiodepressant effects are not known. The main purpose of this work was to correlate the effect of Met-enkephalin on the rate of sympathetic nerve discharge with its cardiodepressant actions. Anesthetized male rabbits (2-3 kg) were instrumented for the measurement of blood pressure, heart rate, electrocardiogram and multiunit renal nerve activity (RNA). Intravenous administration of norepinephrine (15 micrograms/kg) or phenylephrine (50 micrograms/kg) produced a rapid increase in blood pressure followed by a reduction of RNA and heart rate. Met-enkephalin administered via the same route in doses of 1, 10, 100 and 1000 micrograms/kg initially decreased the RNA and subsequently reduced blood pressure. The above effects of Met-enkephalin were antagonized by naloxone (1 mg/kg i.v.) given 10 min before the peptide. Naloxone methobromide (1.3 mg/kg i.v.), a quaternary derivative of naloxone, did not block the effects of Met-enkephalin under identical conditions. These results suggest that the hypotensive effect of Met-enkephalin is secondary to its effects on sympathetic outflow. Lack of naloxone methobromide action is due to its inability to cross the blood-brain barrier and is consistent with a centrally mediated action of Met-enkephalin.