Transient thermal, but not mechanical, hypoalgesia appears at the early stages of the development of an hyperalgesic murine osteosarcoma. This hypoalgesia is suppressed by the administration of naloxone, its peripherally acting analog naloxone methiodide, the mu- and delta-opioid receptor antagonists cyprodime and naltrindole, or the CRF receptor antagonist, alpha-helical CRF (9-41). When immunohistochemical assays were performed with an anti-beta-endorphin antibody, whose in vivo administration suppressed the analgesia, labeled mononuclear immune cells appeared both inside and surrounding the tumoral tissue. In conclusion, the peripheral action of beta-endorphin, released in response to the osteosarcoma seems responsible for the observed thermal analgesia.