Hypophosphatemic osteomalacia that remits after resection of a coexisting tumor has been described in 35 patients. Because the associated neoplasms have been of mesenchymal origin, it has been inferred that this tumor-induced osteomalacia syndrome is uniquely related to tumours of this derivation. However, in the present investigation we studied subjects with coincident hypophosphatemia and prostatic carcinoma to ascertain whether this endodermal malignancy causes the tumor-induced osteomalacia syndrome. The hypophosphatemic patients had renal phosphate wasting, gastrointestinal malabsorption of calcium and phosphate, and negative phosphate balance. Moreover, bone biopsies showed histomorphologic changes indicative of osteomalacia. Although widespread metastases precluded establishing the diagnosis of tumor-induced osteomalacia by resection of the tumor, a series of studied excluded alternate causes for the osteomalacia. Further, affected subjects had a normal serum concentration of 25-hydroxyvitamin D, 28.0 +/- 8.3 ng/mL, and serum 1,25-dihydroxyvitamin D levels were low, 15.0 +/- 1.0 pg/mL, characteristic of the tumor-induced osteomalacia syndrome. Thus, prostatic carcinoma, although an endodermal malignancy, may cause the tumor-induced osteomalacia syndrome.