Central infusion of Na(+)-rich artificial cerebro-spinal fluid (aCSF) activates the brain renin-angiotensin system and causes sympatho-excitatory and pressor responses. We evaluated the role of the subfornical organ (SFO) and angiotensin II type 1 (AT1) receptors in the SFO in mediating the central Na(+)-induced pressor response. In conscious Wistar rats, intra SFO infusions of Na(+)-rich aCSF containing 0.45 and 0.6M Na(+) at 10 nl/min or injection of angiotensin II (Ang II) at 80 ng increased blood pressure (BP) by 15-22 mmHg, whereas mannitol with the same osmolarity as the Na(+)-rich aCSF had no effects. Intra SFO infusion of the AT1 receptor blocker candesartan abolished the pressor response induced by intra SFO administration of Na(+)-rich aCSF or Ang II. Intra cerebro-ventricular (icv) infusion of Na(+)-rich aCSF (0.3M Na(+)) at 3.8 μl/min for 10 min increased BP by 15-20 mmHg. Electrolytic lesion of the SFO attenuated these BP increases by 50-70%. Intra SFO infusion of candesartan also prevented 50% of these pressor responses. These data suggest that SFO neurons are indeed sensitive to Na(+), the SFO is a major - but not only - site in the brain to sense an increase in CSF [Na(+)], and activation of AT1 receptors in the SFO mediates the SFO component of the Na(+)-induced pressor response.