Ethanol is generally believed to inhibit vasopressin (VP) release into the peripheral circulation. The primary evidence for this conclusion has been indirectly based on measurement of classical endocrine responses such as urine formation and electrolyte excretion. We used radioimmunoassay to obtain direct measurements of VP on the plasma of rats. Consistent with previous notions, we found that VP levels were inhibited sixty minutes after intraperitoneal (ip) injection of ethanol. However, five minutes after ethanol administration, plasma VP levels were markedly elevated. Through the use of sensitive radioimmunoassay techniques were able to observe that ethanol is a powerful stimulant for the immediate release of VP into the peripheral circulation. Recent immunohistochemical studies describing immunoreactive-VP containing fibers suggest that, in addition to the peripheral release of VP via classical hypothalamo-hypophyseal pathways, VP is released at a number of extrahypothalamic brain sites and into the cerebroventricular system. There is very little information, however, on the influence of ethanol on VP in these systems. Since VP has been implicated in memory processes and in the development and maintenance of tolerance to ethanol, it is important to determine the effects of ethanol of central, as well as peripheral, release of this neuropeptide. With the use of radioimmunoassay techniques, the current project has been designed to: 1) describe the effects of acute ethanol administration of VP release into the peripheral circulation of rats, 2) examine the effects of acute ethanol administration on VP release into cerebrospinal fluid (CSF), and compare the results to those of the peripheral VP system, 3) begin to explore mechanisms underlying ethanol-induced changes in VP release into plasma and CSF.