Micropuncture experiments were performed in volume-expanded rats to better define the nephron segments in which changes in renal perfusion pressure inhibit tubular reabsorption. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of vasopressin, aldosterone, cortkosterone, and norepinephrine were maintained at fixed levels by i.v. infusion. Fractional excretion of sodium, chloride, and water increased markedly after renal perfusion pressure was elevated from 110 to 150 mm Hg. Renal blood flow, glomerular filtration rate, and single nephron glomerular filtration rate measured from deep and superficial nephrons were unaltered. Reabsorption of chloride and water in the proximal tubule of superficial nephrons decreased by 10% after renal perfusion pressure was elevated and contributed to the pressure-diuretic response. Changes in renal perfusion pressure also altered the reabsorption of water and chloride in juxtamedullary nephrons. The percentage of the filtered water load reaching the tip of the loop of Henle increased from 19.8 ± 2.9 to 38.1 ± 3.0% after renal perfusion pressure was elevated. Chloride delivery rose from 34.2 ± 4.3 to 65.2 ± 4.8% of the filtered load. These results support the view that alterations in medullary hemodynamks participate in the pressure-natriuretk response by inhibiting tubular reabsorption in the proximal tubule or the thin descending limb of the loop of Henle (or both) of juxtamedullary nephrons.