Objective: To determine whether the calculated ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA), a proposed screening test for primary aldosteronism, provides a renin-independent measure of circulating aldosterone that is suitable to judge whether PAC is inappropriately elevated relative to PRA. Subjects and Methods: This study consisting of 221 black and 276 white subjects with previously diagnosed essential hypertension was conducted between 1996 and 2000. Antihypertensive drugs were withdrawn for at least 4 weeks; PAC and PRA were measured while subjects were supine and then seated after 30 minutes of ambulation. The seated measurements were repeated after 4 weeks of oral diuretic therapy with hydrochlorothiazide (25 mg/d). Results: The variation in the aldosterone-renin ratio was strongly and inversely dependent on PRA (R2=0.71; P<.001). When subjects changed position from supine to seated, the increase in mean ± SD PRA (from 1.18±1.06 to 1.31±1.19 ng·mL-1; P<.001) was associated with an increase in the mean ratio (from 18.6±52.8 to 25.8±38.1 h·102; P<.001), whereas the increase in mean ± SD PRA in response to diuretic therapy (from 1.31±1.19 to 2.72±2.67 ng·mL-1·h-1; P=.001) was associated with a decrease in the mean ratio (from 25.8±38.1 to 16.4±31.6 h·102; P<.001). Conclusion: In patients with previously diagnosed essential hypertension, calculation of the aldosterone-renin ratio does not provide a renin-independent measure of circulating aldosterone that is suitable for determining whether PAC is elevated relative to PRA. Because elevation of the aldosterone-renin ratio is predominantly an indicator of low PRA, its perceived value in screening for primary aldosteronism most likely derives from additional diagnostic tests being done in patients with low-renin hypertension.