A 70-year-old white woman had a lower abdominal mass and hypercalcemia. Physical and radiologic evidence was found for the presence of nonmetastatic pelvic tumor. Biochemical tests confirmed the presence of hypercalcemia with evidence of active bone resorption. Plasma parathyroid hormone (PTH) and the nephrogenic urinary cyclic AMP excretion were low; levels of plasma prostaglandins were elevated. Bone biopsy revealed histologic evidence of extensive osteoclastic bone resorption. At operation, a papillary serous cystadenocarcinoma of the ovary was removed. Postoperatively, the serum calcium fell to normal, and plasma prostaglandins became undetectable. Short-term incubation of ovarian tumor fragments demonstrated the production by tumor tissue of a substance causing bone resorption in an in vitro bioassay. The production of this substance was blocked by indomethacin. Radioimmunoassay of the incubation medium revealed significant amounts of prostaglandins of the E + F series. Parathyroid hormone was not detected in the medium. These data implicate tumor-produced prostaglandins as mediators of the hypercalcemia in this patient.