The purpose of this study was to evaluate the involvement of central angiotensin II (ANGII) and AT1 receptors in systemic release of arginine vasopressin (AVP) and blood pressure regulation during endotoxemia. LPS (150 µg/kg) was injected intravenously (i.v.) 30 min after i.c.v. losartan (50 µg), an AT1 receptor antagonist, or s.c. captopril (50 mg/kg), an ANG converting enzyme inhibitor. Rats with i.c.v. and s.c. saline injections served as control. LPS administration increased plasma AVP concentration from 2.1 ± 0.2 to 15.2 ± 2.5 pg/ml (60 min after LPS injection) without significant changes in plasma osmolality or hematocrit. LPS-induced AVP secretion was significantly attenuated by pretreatment with i.c.v. losartan (2.3 ± 0.5 to 3.7 ± 0.5 pg/ml), but was not attenuated after peripheral captopril treatment (2.2 ± 0.6 to 17.6 ± 4.2 pg/ml). LPS administration significantly decreased SBP by 22.7 ± 5.4 mmHg after i.v. LPS injection in losartan-treated rats, while SBP remained unchanged in vehicle-treated or captopril-treated rats by i.v. LPS. These results indicate that central AT1 receptors, not responsive to peripheral ANGII, play an important role in systemic AVP secretion and maintenance of blood pressure during endotoxemia.