The effect of varying concentrations of substrate-free albumin (SFA) in the absence of exogenous substrate was investigated in the isolated perfused rat kidney. Consistent with starling relationship, there was a progressive decrease in glomerular filtration rate (GFR), from 778 ± 36to41 ± 17 µl/min · g, and a progressive increase in fractional sodium reabsorption (%TNa+), from 31.1 ± 0.9 to 82.6 ± 2.3%, when the mean SFA concentration in the perfusate was increased from 3 to 10 g/dl. Perfusate flow rate (PFR) remained constant at 30 ml/min · g as the GFR decreased. When the mean perfusate SFA concentration was decreased from 3 g/dl to 0, the anticipated decrease in %TNa+ occurred but the increase in GFR did not. PFR was also reduced by one half when SFA was not present in the perfusion medium. The reason for the anomalous behavior of GFR and PFR when SFA was omitted from the perfusion medium is not clear.