Dexamethasone-suppression (DS) adrenal scintigraphy localizes an aldosteronoma, but with false-negative results, i.e. 2 of 19 cases in our study. Our aim was to clarify the clinical meaningfulness of this test. Adrenal iodomethyl-norcholesterol (NP-59) uptake on the adenoma side correlated with the estimated adenoma volume (n = 15, r = 0.843, P less than 0.001). Accordingly, the uptake ratio on the adenoma side to that on the opposite side depended on the adenoma volume (r = 0.683, P less than 0.01). This explains the false-negative results (uptake ratio less than 2) in two cases with small adenomas. The NP-59 uptake correlated weakly with the plasma aldosterone level (r = 0.516, P less than 0.05). This result indicates the low correlation between NP-59 uptake and the ability to secrete aldosterone. NP-59 accumulation in the surgically removed gland was analyzed by autoradiography in six cases where DS scintigraphy was done just before surgery. The density was higher in the adenoma cells than in the adjacent cortical cells in five cases, but the difference was rather small, i.e., within a 2-fold difference in four cases. In one case, almost the same density was observed in both types of cells. Thus, the laterality of NP-59 uptake primarily depends on the adenoma volume although NP-59 uptake somewhat reflects the adenoma's ability to secrete aldosterone or the adenoma cell's activity in accumulating NP-59. Care must be taken in interpreting the findings from DS scintigraphy where the adenoma is small or adrenal uptake is low.