The possibility of active specific immunotherapy using interleukin-1 (IL-1) plus sonicated tumor supernatant (SS) was examined in a murine tumor model. The growth of intraperitoneally or subcutaneously inoculated plasmacytoma MOPC104E, which is syngeneic to BALB/c mice, was significantly suppressed by intraperitoneal pretreatment with IL-1 and SS from MOPC104E cells (MOPC-SS), on days 10, 7, and 4 before tumor inoculation. Pretreatment with IL-1 plus MOPC-SS or MethA-SS (SS from MethA cells) suppressed the growth of subcutaneous tumor of only the corresponding tumor cells, indicating the development of tumor-specific immunity in vivo. The splenic cells of immunized mice with IL-1 and MOPC-SS showed tumor neutralizing activity. However, their tumor neutralizing activity was abrogated when they were treated in vitro with anti-Thy1.2 or anti-L3T4 plus complement. Moreover, when combined with indomethacin per oral, IL-1 plus MOPC-SS significantly suppressed the growth of established subcutaneous tumor and prolonged survival of post-operative mice. These results suggest that this new type of active specific immunotherapy could be a useful method for cancer immunotherapy, especially when combined with oral indomethacin.