In the present study the reduction in renal fractional reabsorption of sodium from 99.6 ± 0.2 to 86.0 ± 3.3 % following ECV expansion with isotonic saline in the rat was associated with a small decrease in renal cortical Na-K-ATPase activity from 12.2 ± 0.5 to 10.8 ± 0.6 µmol Pi/mg protein/h and an increase in medullary enzyme activity from 23.3 ± 1.3 to 28.6 ± 1.8 µmol Pi/mg protein/h. In addition, an increase in cortical ATP concentration from 1.21 ± 0.12 to 1.55 ± 0.10 µmol/g wet weight was observed. These alterations resemble renal metabolic changes induced by low dose ouabain and favor the hypothesis that decreased tubular reabsorption of sodium following ECV expansion may be associated with alterations in active sodium transport.