A direct, rapid, sensitive, and highly specific radioimmunoassay for plasma aldosterone has been developed using aldosterone conjugated to [125I]histamine as ligand and a highly specific aldosterone antiserum. This assay permits the direct measurement of plasma aldosterone without preliminary extraction or purification steps and hence allows a single technician to assay 500 samples in a week. An excellent correlation was obtained between the results of the direct assay and the levels measured after paper chromatography (n = 43, r = 0.99, P less than 0.001) or after extraction (n = 43, r = 0.99, P less than 0.001). The coefficients of variation for intra-assay and inter-assay determinations of samples from a normal plasma pool were 7.6% and 9.3%, respectively.