Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that angiotensin II (AngII) and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of the AngII type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water deprived and water replete male rats. Since PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM), and since PVN disinhibition increases sympathetic activity in part via increased drive of RVLM AT1R, candesartan was also bilaterally microinjected into RVLM. PVN blockade with bilateral microinjections of muscimol, a GABA_A agonist, decreased BP more (P<0.05) in water deprived (-29±8 mmHg) than water replete (-7±2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7±1 mmHg (P<0.05). In water replete rats, however, candesartan did not alter BP (1±1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6±1 mmHg, P<0.05) in water deprived, but not water replete (-1±1 mmHg) rats. In water deprived rats, kynurenate rapidly decreased BP (-19±3 mmHg) significantly more (P<0.05) than in water replete (-4±1 mmHg) rats. Finally, as in PVN, RVLM candesartan slowly decreased BP in water deprived (-8±1 mmHg, P<0.05), but not water replete (-3±1mmHg) rats. These data suggest that activation of AT1 and glutamate receptors in PVN, as well as of AT1R in RVLM, contribute to BP maintenance during water deprivation.