To understand why elderly females are better able to tolerate hyponatremia, we measured brain Na-K-ATPase activity to determine whether this adaptive mechanism was affected by age. Using synaptosomes from 2-, 12-, and 19-mo-old female rats, we show in our results that Na-K-ATPase activity changes with age in female rats. Enzyme activity was significantly (P = 0.0026) reduced (17%) from 0.416 ± 0.01 at 2 mo to 0.345 ± 0.01 at 12 mo and reduced (P = 0.0001) (34%) to 0.274 ± 0.02 µmol · min¹ · mg protein¹ at 19 mo. To determine whether this decrease was due to reduced transport function of the Na-K-ATPase pump, we performed potassium transport using rubidium (⁸⁶Rb⁺) as tracer. Ouabain-sensitive potassium uptake at 2 mo was 16.18 ± 1.31 nmol/mg protein, was significantly (P = 0.0063) reduced (39%) to 9.79 ± 1.44 nmol/mg at 12 mo, and was significantly (P = 0.0003) reduced (62%) to 6.12 ± 1.05 nmol/mg protein at 19 mo. On the contrary, Na-K-ATPase activity remained elevated in males during aging. These data suggest that the Na-K-ATPase pump in female rat brain synaptosomes is decreased with increased age, and that this decrease is probably due in part to decreased potassium transport by the Na-K-ATPase pump.