Available data suggest that ionized calcium may interact with a cell surface "sensor" or "receptor" to produce changes in one or more intracellular second messengers that ultimately regulate the release of parathyroid hormone (PTH). Recently, we developed a series of monoclonal antibodies directed toward specialized differentiation antigens expressed on endocrine cells. Since many of these monoclonal antibodies displayed exquisite specificity for cell surface molecules on the parathyroid cell, we used these reagents as probes to investigate signal recognition/transduction mechanisms associated with abnormal calcium-regulated PTH secretion. Depending on their binding site on the respective target antigen molecules, these monoclonal antibodies either stimulated or inhibited hormone secretion. Thus, defects in membrane-associated structures may contribute to deranged calcium-regulated PTH secretion in abnormal parathyroid cells.