Osteoid osteomas are characterized clinically by a pattern of nocturnal pain which is exquisitely sensitive to salicylates. Etiology for the pain has been ascribed by previous investigators to the presence of nonmyelinated nerve fibers or to the effect of prostaglandins. In an effort to corroborate the potential role of prostaglandins in mediating the pain associated with this tumor, we have determined the concentration of prostaglandins E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 utilizing radioimmunoassay of extracts of homogenated tumor tissue. Results were compared with similar extracts of normal bone and a variety of other osseous tumors. The increased concentrations of prostaglandin E2 found in cases of osteoid osteoma and osteoblastoma confirm studies of explants of these tumors previously recorded in the literature.