SUMMARYIn order to investigate the effect of chronic sodium depletion on renal proximal tubular reabsorption, studies were performed in conscious, unrestrained Brattleboro rats. Since these animals lack circulating vasopressin, fractional water reabsorption in the distal nephron can be assumed to be constant and changes in urine flow rate should therefore reflect changes in endproximal fluid delivery. Sodium depletion was induced by placing rats on a low-sodium diet (4 mmol Na (kg dry wt)-1) and administering frusemide (40 mg (kg body wt)-1) by gavage on the first 2 days. Extracellular volume, measured after 7-9 days, was reduced by 19 % (P < 0 02) as compared with that of rats maintained on a control diet. Urine flow rate, measured during days 4-7 of the low-sodium diet, was significantly lower than that of control rats (142 + 8 vs. 168 + 5 ml day-', P < 0 01). Since renal papillary interstitial fluid osmolality was found to be reduced in the sodium-depleted rats (693 + 38 vs. 812 + 36 mosmol (kg H2O)-', P < 0 05), it is unlikely that water reabsorption from sites beyond the proximal tubule had increased. The observed reduction in urine flow rate therefore strongly suggests a reduction in end-proximal fluid delivery. In the second part of the study, a single group of Brattleboro rats was used, in which osmotic minipumps were implanted in the peritoneal cavity for continuous infusion of[14C]inulin. After recovery from the operation, the rats were maintained on a control diet for 6 days (pre-control period), then subjected to sodium depletion (low-sodium diet for 6 days, frusemide administration on the first 2 days), and finally returned to the control diet for 6 days, with access to 0 46 M NaCl solution on the first 2 days, in order to restore sodium balance (postcontrol period). On the final 2 days of each phase, urine flow rate and [14C]inulin clearance (= glomerular filtration rate, GFR) were measured. Urine flow rates during the pre-control, sodium depletion and post-control periods were 169+7, 132+8 (P<0-001) and 176+8 1l min-1, respectively; corresponding values for fractional water excretion were 7 0 + 0 3, 6 0 + 0 5 (P < 0 01) and 7-4 + 0 4 %. Only a small reduction in GFR, of borderline statistical significance, was observed during sodium depletion. We conclude that chronic sodium depletion causes a reduction in end-proximal fluid delivery which is largely a consequence of enhanced fractional fluid reabsorption in the proximal tubule.