The effects of intracarotid injection of morphine and naloxone on plasma vasopressin levels and arterial blood pressure were examined in pentobarbital-anesthetized dogs. Morphine administration decreased blood pressure in a dose-dependent fashion with a threshold between 10 and 50 micrograms/kg. Plasma levels of vasopressin rose in parallel with the decrease in blood pressure and were significantly elevated after doses of 50 and 100 micrograms/kg of morphine. Intracarotid injection of the opioid antagonist naloxone (1 mg/kg) increased blood pressure slightly, but significantly, and increased plasma concentrations of vasopressin approximately 60%. Pretreatment with naloxone did not blunt the hypotensive effect of morphine at a dose of 50 micrograms/kg, but enhanced the secretion of vasopressin in response to the morphine stimulus; plasma vasopressin levels were 5-fold greater than those found in animals given morphine but not pretreated with naloxone. Pretreatment with the histamine receptor blockers chlorpheniramine and cimetidine blunted morphine-induced (50 micrograms/kg) hypotension by about 50% and prevented a significant increase in the plasma vasopressin concentration. The data are consistent with the hypothesis that stimulation of vasopressin secretion by systemically administered morphine is secondary to the blood pressure fall. However, it also appears that, in the pentobarbital-anesthetized dog, naloxone-sensitive systems exert a tonic inhibitory influence over both vasopressin secretion and blood pressure.