This study evaluated whether pressure-diuretic and pressure-natriuretlc responses are associated with alterations in vasa recta hemodynamics. Autoregulation of cortical and papillary blood flow was studied using a laser-DoppIer flowmeter in volume-expanded and hydropenk rats. Superficial cortical flow and whole kidney renal blood flow were antoregulated in volume-expanded rats and decreased by less than 10% after renal perfusion pressure was lowered from 150 to 100 mm Hg. In contrast, papillary blood flow was not autoregulated and fell by 24 ± 2%. The failure of papillary blood flow to autoregulate was due to changes in the number of perfused vessels as well as to alterations In blood flow in individual ascending and descending vasa recta. Pressure hi vasa recta capillaries increased from 6.8 ± 0.8 to 13.8 ± 1.2 mm Hg after renal perfusion pressure was elevated from 100 to 150 mm Hg, and renal Interstitial pressure rose from 7.4 ± 0.8 to 12.3 ± 1.4 mm Hg. In hydropenic rats, papillary blood flow was autoregulated to a significant extent, but it still decreased by 19% after renal perfusion pressure was lowered from 150 to 100 mm Hg. The pressure-diuretic and presure-natriuretic responses in hydropenic rats were blunted in comparison to those observed in volume-expanded rats. These findings indicate that the pressure-diuretic and pressure-natriuretic responses are associated with changes in vasa recta hemodynamics and renal interstitial pressure.