The effect of leucine5-enkephalin (Leu-enkephalin) administered into the lateral (LV) or fourth (4V) cerebroventricle on angiotensin II (ANG II)-stimulated increase in blood pressure, plasma vasopressin concentration ([AVP]), and drinking behavior was determined in conscious rats. Leu-enkephalin (20, 50, or 100 micrograms) was injected into the LV (5 microliters) or 4V (2 microliters) less than or equal to 15 s before ANG II (50 or 500 ng, LV). LV and 4V administration of Leu-enkephalin (100 or 50 micrograms) significantly (P less than 0.05) delayed the drinking onset, decreased the number of animals drinking, and reduced the volume consumed (100 micrograms, 30 min) in response to ANG II (50 ng). ANG II-stimulated increases in plasma [AVP] and blood pressure were inhibited by 50 or 100 micrograms, respectively, of Leu-enkephalin administered into LV but not 4V. Decreased motor activity occurred after Leu-enkephalin (100 micrograms) administration into LV and 4V, whereas head shakes were more consistent after the former. Fast green dye administered into 4V did not reach anterior periaqueductal, third, or lateral cerebroventricular sites. Thus opioid peptide receptors inhibiting ANG II-stimulated drinking, vasopressin release, and pressor response are postulated to be in brain structures accessible from lateral or third cerebroventricles. Opiate receptors inhibitory to drinking are also reached from peri-4V sites.