Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood (obtained by venous catheterization) from patients with hyperparathyroidism, as well as from calves and from cattle. Hormone secreted in vivo from normal bovine parathyroid glands and from human parathyroid adenomas is similar in size to the 84-amino-acid peptide (molecular weight of 9500) extracted from the parathyroids. However, much of the immunoreactive parathyroid hormone present in the peripheral circulation of man and cattle is smaller than the extracted or secreted hormone; it elutes from gel columns at a position corresponding to a molecular weight of about 7000. The immunological characteristics of extracted and secreted hormone are identical, while hormone in the general circulation is immunologically dissimilar to extracted and secreted hormone. The results indicate that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.