Previous studies have established that during orthograde perfusion from a late proximal tubule site, there is a direct relationship between the magnitude of the feedback response and the level of distal tubular fluid sodium chloride concentration. The present study was conducted in the rat to extend this observation by assessing stop flow pressure (SFP) feedback responses during retrograde perfusion into the early distal tubule with solutions varying in total solute concentration and in the anionic constituent. SFP was measured after blockade of the intermediate proximal and late distal tubular segments with wax. Retrograde perfusion was initiated from an early distal tubular site at 15 nl/min. All solutions contained a 38 mOsm/kg matrix base, and the total solute concentration was increased with either sodium chloride or sodium isethionate to achieve osmolalities of 68, 85, and 120 mOsm/kg. For comparison, feedback responses during perfusion with a 120 mOsm/kg choline chloride solution were evaluated. During perfusion with the 120 mOsm/kg solutions, SFP decreased by 13 +/- 1.3 mm Hg with the sodium chloride solution, 12 +/- 1.5 mm Hg with the sodium isethionate solution, and 12 +/- 1.3 mm Hg with the choline chloride solution. During perfusion with solutions having an osmolality of 85 mOsm/kg, SFP decreased by 8 +/- 1.3 mm Hg with sodium chloride and 8 +/- 0.8 mm Hg with sodium isethionate. The 68 mOsm/kg solutions elicited decreases in SFP of 4.4 +/- 0.4 mm Hg and 5 +/- 0.5 mm Hg. During perfusion with the 38 mOsm/kg matrix solution, SFP decreased by an average of 1.4 +/- 0.9 mm Hg. Linear regression analysis revealed a 1 mm Hg decrease in SFP for every 7.7 mOsm/kg decrease in perfusate osmolality below 120 mOsm/kg. These results confirm previous findings that the magnitude of the feedback response is associated closely with the concentration of the perfusate over a narrow range from 38 to 120 mOsm/kg. Since the responses with sodium isethionate solutions were similar to the responses obtained with sodium chloride containing solutions, these studies provide evidence that the magnitude of the feedback responses are not specifically dependent on alterations in chloride concentration.