It is well known that IL-4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL-4 genemodified tumor vaccine were investigated. The mice were vaccinated with the IL-4 gene-modified B16 melanoma cells. Then the proliferative capacity of the splenic lymphocytes, the levels of the antibodies in the murine serum against wild-type B16 cells and the cytotoxicity of the serum to wild-type melanoma cells were detected. Our data showed that the LPS-induced proliferation of the splenic lymphocytes from the mice vaccinated with the IL-4 gene-modified tumor vaccine increased more significantly than that from mice vaccinated with wildtype tumor vaccine. The cytotoxicity of the serum to wildtype melanoma cells also increased markedly when detected. It was also observed that the number of pulmonary metastases decreased more obviously when the mice were intravenously injected with the mixture of wild-type B16 cells and the serum from the mice vaccinated with the IL-4 gene-modified B16 cells. Our data demonstrated that humoral immunity might contribute to the antitumor effect of IL-4 gene therapy.