I. Introduction THE ROLE of PTH as a major physiological regulator of calcium homeostasis has been studied extensively, and both bone and kidney have long been recognized as classical major target organs for PTH action (1, 2). More recently, however, evidence has accumulated which indicates that PTH has diverse biological effects in other tissues as well. For example, in the gastrointestinal tract, PTH has been reported to act directly to stimulate calcium transport in the chick duodenum (3) and to increase gastrin release from the pig stomach (4, 5). As discussed in detail later, PTH also is an inhibitor of smooth muscle contraction in the cardiovascular system, in the gastrointestinal (GI) tract, and in other tissues such as trachea, uterus, and vas deferens. In the central nervous system, immunoreactive PTHlike activity has been detected in human cerebrospinal fluid, and its release has been reported from the pituitary and from different regions of the brain of a variety of vertebrates, including mammals (6–11). PTH also has been shown to stimulate cAMP accumulation in cultured murine glioblasts (12). In other in vitro experiments, PTH elicited corticosteroidogenesis in rat adrenocortical cells (13) and stimulated mitosis in rat thymic lymphocytes (14). At present, the physiological significance of these varied effects and the mechanisms of action of PTH in these tissues remain to be elucidated. Furthermore, the recent discovery of a PTH-related protein (PTHrP) (15–17), which has N-terminal homology with PTH and acts like PTH on bone, kidney, and other tissues, raises the question of whether PTHrP serves as an endogenous regulator of some of the nonclassical effects uncovered using PTH.