Recent advances in our understanding of the regulation of parathyroid hormone secretion in vivo and in vitro are reviewed. The use of assays specific for immunoreactive intact parathyroid hormone has greatly improved our capacity to study parathyroid hormone dynamics in vivo. Such studies have emphasized the steep, inverse sigmoidal relationship between circulating intact parathyroid hormone and serum ionized Ca2+concentrations, which can be modulated in a reciprocal fashion by 1,25 dihydroxyvitamin D. The use of the intact assay has also revealed additional complexities in the control of parathyroid hormone dynamics in vivo, including circadian and pulsatile patterns in parathyroid hormone as well as hysteresis and rate dependence in the relationship between intact parathyroid hormone levels and Ca2+. Studies in vitro have emphasized the role of a putative, extracellular Ca2+receptor in regulating parathyroid function that is coupled by one or more G proteins to intracellular second messengers and parathyroid hormone secretion. Finally, the regulation of parathyroid hormone gene expression by extracellular Ca2+and 1,25 dihydroxyvitamin D has been clarified at a molecular level by the description of specific motifs in the upstream region of the parathyroid hormone gene that mediate binding of specific inhibitory nuclear factors.