To develop a simple screening and diagnostic test for primary aldosteronism and to compare it with established techniques. Comparison of several techniques for screening, diagnosis, and differentiation of primary aldosteronism using normotensive and hypertensive subjects. Four hundred thirty-four normotensive subjects, 263 essential hypertensive subjects, 48 subjects with primary aldosteronism due to a unilateral adrenal adenoma, and 14 in whom primary aldosteronism was associated with findings of bilateral hyperaldosteronism were studied. Plasma renin activity and plasma aldosterone were measured in venous blood obtained at 8 AM after 2 hours of ambulation and compared with established suppressive (plasma aldosterone) and stimulatory (plasma renin activity) maneuvers used for the diagnosis of primary aldosteronism. The ratio of plasma aldosterone to plasma renin activity provided complete separation of patients with primary aldosteronism from the normal and essential hypertensive groups. Moreover, based on the use of traditional localizing procedures separating unilateral hyperaldosteronism due to a solitary adenoma from bilateral hyperaldosteronism, confirmed by surgical intervention in the former subgroup, the ratio provided differentiation of these two forms of primary aldosteronism. The use of the plasma aldosterone to plasma renin activity ratio appears to be useful in the screening, diagnosis, and differentiation of unilateral and bilateral forms of primary aldosteronism. These observations may also be applicable to patients receiving some antihypertensive medications.