Extracellular fluid volume expansion is associated with a decrease in the transepithelial chloride gradient in the proximal convoluted tubule. We have previously shown that this effect occurs in the presence of hypo- or hyperchloremia and is not dependent on a change in filtered chloride or bicarbonate load. To determine the influence of filtered fluid load on this effect of volume expansion, micropuncture studies were carried out during acute extracellular fluid volume expansion in rats with (group AC) and without (group CON) a reduction in renal perfusion pressure. Delayed aortic constriction prevented the increase in fluid load (49.7 +/- 2.4 and 49.0 +/- 3.9 nl/min for hydropenia and volume expansion, respectively), but reduced tubule fluid to plasma inulin ratios (2.25 +/- 0.13 and 1.84 +/- 0.8) were maintained. Tubule fluid to plasma chloride ratios did not change in group AC (1.27 +/- 0.03 and 1.25 +/- 0.01) as compared to group CON (1.25 +/- 0.02 and 1.18 +/- 0.02; p less than 0.05). Fractional chloride reabsorption fell in both groups. Absolute chloride reabsorption was highly correlated (p less than 0.001) with absolute fluid reabsorption. These results suggest that filtered fluid load or some related variable is an important determinant of the generation of the chloride gradient in the proximal tubule.