Renal blood flow is modulated by renal sympathetic nerve activity (RSNA). However, agents that are supposed to reduce sympathetic tone, such as rilmenidine and captopril, influence renal blood flow also by direct arteriolar effects. The present study was designed to test to which extent the renal nerves contribute to the renal hemodynamic response to rilmenidine and captopril. We used a technique that allows simultaneous recording of renal blood flow (RBF) and RSNA to the same kidney in conscious rabbits. We compared the dose-dependent effects of rilmenidine (0.01-1 mg/kg) and captopril (0.03-3 mg/kg) on RBF and RSNA in intact and renal denervated (RNX) rabbits. Because rilmenidine and captopril lower blood pressure, studies were also performed in sino-aortically denervated (SAD) rabbits to determine the role of the baroreflex in the renal hemodynamic response. Rilmenidine reduced arterial pressure, RBF and RSNA dose-dependently. In intact rabbits (n=10) renal conductance (RC) remained unaltered (3±5%), even after the 1 mg/kg dose which completely abolished RSNA. In RNX rabbits (n=6) RC fell by 18±5%, whereas in SAD rabbits (n=7) RC increased by 30±20 % after rilmenidine. In intact rabbits, captopril increased RSNA maximally by 64±8 %. RSNA did not rise in SAD rabbits. Despite the differential response or absence of RSNA, captopril increased RC to a comparable degree (maximally 40-50%) in all three groups. Using spectral analysis techniques we found that in all groups, independent of ongoing RSNA, captopril, but not rilmenidine, attenuated both myogenic (0.07-0.25 Hz) and tubuloglomerular feed-back (0.01-0.07 Hz) related fluctuations in RC. We conclude that, in conscious rabbits, the renal vasodilator effect of rilmenidine depends upon the level of ongoing RSNA. Its sympatholytic effect is, however, blunted by a direct arteriolar vasoconstrictor effect. In contrast, the renal vasodilator effect of captopril is not modulated by ongoing RSNA and is associated with impairment of autoregulation of RBF.