Stimulation of bone resorption by local factors, the cytokines, is key to the development of hypercalcemia in multiple myeloma patients. Parathyroid hormone-related peptide, the systemic factor found in humoral hypercalcemia, has rarely been incriminated in myeloma. We report a case of myeloma with hypercalcemia and elevated serum level of parathyroid hormone-related peptide. Bisphosphonate therapy was rapidly effective in correcting serum calcium levels despite persistent high levels of the peptide. Seven other cases of myeloma with hypercalcemia and high serum parathyroid hormone-related peptide levels have been reported. Expression by myeloma plasmocytes of the messenger RNA for this peptide has also been demonstrated. These data suggest that parathyroid hormone-related peptide may contribute to the development of hypercalcemia in some myeloma patients.