Plasma ouabain-like immunoreactivity, which has been supposed to be associated with hypertension, was significantly higher in five patients with primary aldosteronism than in age-matched normotensive subjects. High plasma levels of ouabain-like immunoreactivity decreased to normal after removal of adenoma. Extracts of adenoma tissue did not contain any apparent ouabain-like immunoreactivity. Anti-ouabain antibody used in this study did not cross-react with aldosterone, cortisol, corticosterone, arachidonic acid or lysophosphatidylcholine. Hypertension, hypokalemia, a high plasma aldosterone level and low plasma renin activity were also normalized after surgery. These results indicate that hyperaldosteronism induces the high plasma level of ouabain-like immunoreactivity and this is associated in part with high blood pressure (BP) in primary aldosteronism.