We have previously shown that a chimeric IgE antibody against the folic acid receptor (MOv18 IgE) inhibits tumor growth in a SCID mouse model of ovarian carcinoma. MOv18 IgE gave greater protection than the corresponding chimeric MOv18 IgG1. We have now confirmed these effects in a nude-mouse model of ovarian carcinoma and have demonstrated for the first time that human monocytes are active in IgE antibody-dependent cell-mediated cytotoxicity. Injection of tumor-bearing mice with PBMC and MOv18 IgE led to infiltration of monocytes into the tumors and prolonged survival of the mice. Incubation of PBMC or purified monocytes and MOv18 IgE with ovarian tumor cells in vitro resulted in tumor cell killing proportional to the expression of unoccupied FcepsilonRI on monocytes.We observed phagocytosis of tumor cells by the monocytes in vitro. Our results suggest that tumor-specific IgE antibodies may be exploited for immunotherapy of cancer.