Sodium permeability (P22Na) and steady state transepithelial concentration differences of Na (delta cNa) were measured in stationary droplets in proximal tubules of rats in both the non-expanded (NE) and subsequent mannitol-saline volume-expanded (VE) state. The test solutions for tubular injection were either an artificial tubular solution (AS) in group I rats or harvested proximal tubular fluid (HTF) in a second group of rats (group II). delta cNa (mmol.kg-1H2O) was significantly reduced (p less than 0.001) with HTF in the VE state (12.1 +/- 0.8 SEM) when compared to HTF in the NE state (17.8 +/- 1.8) and AS in both NE (17.4 +/- 1.0) and VE (18.2 +/- 1.0). P22Na calculated from the half-time of disappearance of 22Na from the droplets, when using paired experiments were 8.1 +/- 1.7 X 10(-5) mm2.sec-1 and 7.3 +/- 1.8 with HTF in NE and subsequent VE and 8.6 +/- 1.1 and 7.7 +/- 0.8 with AS in NE and VE. These permeability results did not differ from each other significantly. In these experiments with zero net Na and water fluxes, the 32% reduction of delta cNa cannot be accounted for by an increased backleak of Na, since P22Na would have had to increase by 32%. These results therefore provide strong evidence for a factor present in proximal tubular fluid consequent upon VE which inhibits Na transport without altering transepithelial PNa, but do not exclude an effect of such a factor on the cellular Na entry step or the Na pump itself.