Twenty-two consecutive cases of adenoma in acromegalic patients were studied immunohistochemically. All the tumors contained prolactin (PRL)-reactive cells (3% to 53% of the total number of tumor cells) as well as growth hormone (GH)-reactive cells (4% to 74% of the total number of tumor cells). All acromegalic cases studied were thus plurihormonal adenomas containing GH and PRL; no pure GH cell adenoma was present. Twenty cases were further examined at the ultrastructural level in conjunction with postembedding double-labeling immunoelectron microscopy; 15 of these cases were diagnosed as mixed GH cell-PRL cell adenomas. The previously diagnosed pure GH cell adenomas possibly may have contained PRL cells and thus should be considered as mixed GH cell-PRL cell adenomas. Mammosomatotroph adenomas were rare in this series. Double-labeling immunoelectron microscopy, using protein A gold particles of two different sizes, greatly facilitated the distinction among GH, PRI, and mammosomatotroph cells.