Four monoclonal anti-parathyroid antibodies were generated after immunization of mice with intact cells from human parathyroid tissue. All four monoclonal antibodies reacted in immunohistochemistry with structures present on parathyroid epithelial cells and proximal-tubule cells of the kidney but were unreactive with all other human tissues investigated. Immunofluorescence microscopy on suspended human parathyroid cells showed that the antibodies reacted with structures present on the cell surface. Two of these antibodies efficiently blocked the increase in cytoplasmic calcium concentration of parathyroid cells that is normally associated with increased concentrations of extracellular calcium. The results indicate that these two antibodies interfere with a calcium-sensing mechanism of parathyroid cells--i.e., a potential calcium receptor by which extracellular calcium regulates cytoplasmic calcium and hormone release in these cells.