Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+, K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+, K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li++-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p< 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 ± 0.29 vs 1.51 ± 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 ± 1.5 vs 6.7 ± 1.9 mM) and the number of the Na+, K+-ATPase sites per RBC (331 ± 52 vs 385 ± 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p< 0.001) increase in the rate constant (1.60 ± 0.12 × 10−15vs 1.28 ± 0.15 × 10−15mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p< 0.01) after treatment.