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 postoperative 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. © 1996 Wiley‐Liss, Inc.