We investigated the association of dietary salt and angiotensin-II infusion on hypertension and superoxide formation in the RVLM. Male Wistar rats were subcutaneously infused with Ang-II (150ng/kg/min) or saline (0.9% NaCl) for 14days. In addition, rats had free access to drinking water containing 0.4% or 2.0% NaCl. On the 15th day, rats that received Ang-II+0.4% NaCl exhibited higher levels of baseline arterial blood pressure than rats that received saline+0.4% NaCl (118+/-5mm Hg vs 98+/-4mm Hg, n=9, P<0.05). Rats that received Ang-II+2% NaCl had a significantly greater hypertension compared to Ang-II+0.4% NaCl (165+/-7mm Hg vs 118+/-5mm Hg, n=10, P<0.05). On the other hand, rats treated with saline+2% NaCl or saline+0.4% NaCl did not become hypertensive (96+/-5mm Hg, n=8 and 98+/-4mm Hg, n=7, respectively). Furthermore, administration of hexamethonium (30mg/kg i.v.) evoked larger decreases in mean arterial pressure in rats treated with Ang-II+2% NaCl and rats treated with Ang-II+0.4% NaCl (-100+/-5 Deltamm Hg and -72+/-10 Deltamm Hg, P<0.05). The magnitude of superoxide formation measured by the dihydroethidium technique in the RVLM was greater in the RVLM of rats treated with Ang-II+2% NaCl (123+/-10 Delta%, P<0.05%), than with Ang-II+0.4% (67+/-9 Delta%) and saline+2% NaCl (5+/-3 Delta%,). The findings indicate that dietary salt potentiates Ang-II-derived superoxide formation in the RVLM, resulting in a more severe hypertension. We suggest that this effect could be mediated by an increase in inputs within the forebrain-PVN-RVLM axis.