Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasoconstrictive properties. Biochemical and recent histochemical studies have shown that this peptide is present in human adrenal cortex. This study was intended to determine ET-1 immunoreactivity in human adrenal cortex and cortical adenoma, and hyperplasia ultrastructurally. Light microscopical examination confirmed recent findings of ET-1 immunoreactivity in the three cortical zones (but not in the medulla) as well as in cortical adenoma and cortical hyperplasia. The immunoreactivity in the cortex and adenoma appeared in the cytoplasm in the form of vacuolar structures and grains. Focally, the cell membranes also showed immunoreactive staining. Electronmicroscopical investigation revealed ET-1 immunoreactive products adjacent to the outer surface of the membrane of lipid bodies, in mitochondria and rough endoplasmic reticulum and focally on the cell membrane, but no immunolabeling was seen in the medulla. The localization of ET-1 in the endoplasmic reticulum indicates that this peptide is synthesized in the cortical cells. Its localization in the membrane of the lipid bodies and in the mitochondria suggests that it takes part in synthesis and/or secretion of steroid hormones. The focally immunolabeled cell membranes may be dependent on ET-1 binding to ET receptors.