The tissue distribution of Cu/Zn- and Mn-superoxide dismutases (SOD) in adrenal tumors was studied by an immunohistochemical technique, and the concentrations of both SODs were measured by a sensitive sandwich enzyme immunoassay technique. In the normal adrenal gland, both Cu/Zn- and Mn-SODs were localized predominantly in the reticular zone of the cortex. Cu/Zn-SOD was stained clearly in the inner fascicular zone of the cortex, but not in the medulla, whereas Mn-SOD was stained weakly in the medulla. In different adrenal tumors, the localization of both stained SODs reflected the origin of the tumor cell. Thus, in one section of a pheochromocytoma only Mn-SOD was stained clearly. The concentrations of both SODs in the tissues of medullary tumors were lower than those in the normal adrenal gland and adrenocortical adenomas. The concentration of Cu/Zn-SOD in the tumor tissue of Cushing's syndrome adenoma was higher, and that of Mn-SOD was lower than the concentrations in the normal adrenal gland. The ratio of the tissue concentrations of Mn-SOD to Cu/Zn-SOD was lower in adrenal medullary tumors and Cushing's syndrome adenomas than in the normal adrenal gland and primary aldosteronism adenomas, indicating the predominance of Cu/Zn-SOD in the former, and Mn-SOD in the latter. These data suggest that the localization of Cu/Zn- and Mn-SODs in adrenal tissues reflects the specificity of the adrenal cells that produce the tissue-specific hormones. An investigation of changes in these enzymes in adrenal tumors may also provide useful information on adrenal tumor cell differentiation.