Parathyroid glands from 50 cases of primary hyperparathyroidism were examined by light and electron microscopy in an attempt to elucidate the diagnostic role of electron microscopy in this disease. In the cases in which only one gland was removed at surgery, a final diagnosis by light microscopy was not possible. The electron microscopic findings for some of these single glands (e.g., ribosomal-lamellar complexes and groups of centrioles) suggested that they were adenomas. In cases in which two or more enlarged glands were removed, a correct final diagnosis could be made on the basis of the light microscopic findings alone, and electron microscopy provided no further significant information. Where one enlarged gland and one normally sized gland were removed, electron microscopy disclosed important findings in the normally sized glands. Specifically, light microscopic examination of normally sized glands suggested endocrine suppression, while electron microscopy showed chief cell activity, thereby changing the final diagnosis from adenoma to hyperplasia. The clinical follow-up assessment in some of these patients confirmed the electron microscopic findings. Therefore, the incidence of adenoma in patients with primary hyperparathyroidism should be critically re-evaluated by ultrastructural studies of the normal glands that should be removed with the enlarged ones.