Within recent years newly acquired knowledge has provided a clearer understanding of some aspects of the complex mechanisms that collectively maintain calcium homeostasis within body fluids and it is our intent to define current concepts of the interrelationship of these various factors to the end that fuller understanding may be available concerning the maintenance of calcuim homeostasis in health as well as features which result in its disruption and the consequent effects of imbalances of calcium in various disease states. In this first section dealing with the physiologic state, there are included descriptions of: (1) the metabolism of vitamin D, the synthesis of its active metabolites, 25 OHD3 and1.25(OH)2D3, and the metabolic actions of the active vitamin D metabolite and analogues upon gastrointestinal, bone, and kidney functions; (2) the synthesis, secretion, and metabolic activity of parathyroid hormone and the difficulties with the radioimmunoassay of PTH related to the number of PTH-like peptides in the circulation; and (3) the chemistry, metabolism, and biologic activities of calcitonin, a hypocalcemic principle derived from the parafollicular cells of the thyroid gland. It is emphasized that under normal circumstances these humoral mechanisms act in an integrated manner to maintain serum concentrations of total and ionized calcium within narrowly defined limits.