Several lines of evidence support the existence of an oligosynaptic projection from the paraventricular nucleus of the hypothalamus (PVN) to the kidney in the rat. We sought to provide evidence that this neural pathway is capable of influencing renal function in rats. Bilateral microinjections of bicuculline (Bic; 1 nmol) into the PVN decreased glomerular filtration rate (59%), effective renal plasma flow (71%), urine flow (UV; 57%), and urinary sodium excretion (U_NaV; 54%), accompanied by increased mean arterial pressure (17%) and heart rate (17%). These results were not obtained when Bic was injected outside the PVN or when vehicle (0.9% saline) was injected into the PVN. Bilateral renal denervation (5-7 days before the experiments) significantly reduced the renal vasoconstriction, attenuated the antidiuresis, and abolished the antinatriuresis evoked by PVN stimulation. On the other hand, both the antidiuresis and antinatriuresis evoked by PVN stimulation were undiminished after treatment with either of two vasopressin receptor antagonists ([-mercapto-,-cyclopentamethylenepropionyl¹,O-Et-Tyr²,Val⁴,Arg⁸]vasopressin, a vasopressin V₁ receptor antagonist, or [adamantaneacetyl¹,O-Et-D-Tyr²,Val⁴,aminobutyryl⁶,Arg^8,9]-vasopressin, a V₂ receptor antagonist). In renal-denervated rats treated with the same V₂ receptor antagonist, PVN stimulation produced highly variable increases in both UV and U_NaV, which overall were not statistically different than zero. We conclude that the activation of neurons in PVN evokes 1) renal vasoconstriction accompanied by antinatriuresis, both of which are attributable to the renal nerves, and 2) decreased water excretion, which is mediated by the renal nerves and vasopressin V₂ receptors.