The rat has two parathyroid glands closely associated with the thyroid gland. The parathyroid glands are composed of a single type of peptide secretory cell or a chief cell that forms cords or nests of cells in close apposition to a capillary network. The chief cells secrete parathyroid hormone (PTH) formed in cytoplasmic secretory granules to finely regulate serum ionized calcium and phosphorus concentrations. Low serum calcium stimulates synthesis and secretion of PTH. The cytoplasmic volume of the chief cells predicts the level of PTH production. Chief cells in atrophied glands have little cytoplasm and more prominent stroma. Chief cells in active, hyperplastic, or neoplastic glands have greater cytoplasmic volume. Diffuse hyperplasia can occur secondary to renal failure or calcium and phosphorus imbalances. Rats have a low incidence of spontaneous or toxin-induced multifocal hyperplasia, adenoma, or carcinoma formation. Most chief cells tumors in rats are considered inactive and do not induce the clinical syndrome of hyperparathyroidism.