In parathyroid glands removed from patients with primary hyperparathyroidism (pHPT), hyperplasias and adenomas cannot be distinguished from one another by light microscopy when only one gland is available for examination. When a second gland is available, it is necessary to establish whether it is normal, suppressed, or hyperplastic. This distinction may be difficult, and the main criterion is the amount of cytoplasmic lipid in the parenchymal cells. If the lipid is abundant, the gland is considered normal or suppressed, and if it is scanty, the gland is interpreted as hyperplastic. We have performed a morphometric ultrastructural study to test the reliability of this criterion. Twenty-five adenomatous glands removed from patients with pHPT, when compared with glands of normal size from euparathyroid patients, showed a significant increase in the parameters indicative of metabolic activity, namely the size of the Golgi apparatus, the amount of rough endoplasmic reticulum, and the length of plasmalemmas. In addition, the amount of cytoplasmic lipid was significantly reduced. Furthermore, 25 glands of normal size removed from the same patients with pHPT showed an amount of lipid similar to that of normal glands from euparathyroid patients. However, all the parameters indicative of metabolic activity were significantly higher than those in glands from euparathyroid patients and comparable to those found in adenomatous glands. These results suggest that in pHPT, normal-size glands are as active as adenomatous glands, regardless of a higher lipid content.