Background: The anti-tumor effects of three mouse mammary tumors transfected to express interleukin (IL) 2 or 4 were evaluated. Methods: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected using high efficiency viral vectors. Wild-type or transfected tumor cells were injected subcutaneously into Balb/c mice and animals were observed for tumor growth. Results: Overall, there was a significant decrease in the incidence and in the size of palpable transfected tumor compared with control tumors. Animals were immunized with wild-type or transfected cells and challenged with wild-type tumor. In these experiments, animals immunized with transfected tumor cells had a significantly lower incidence of tumor and significantly smaller tumors than controls. Similar experiments were performed by immunization with irradiated cells (wild type and transfected), and significant immune protection was induced. Conclusions: Each cell line responded differently following gene transfection, with the greatest anti-tumor effects seen in the EMT6 tumor cells transfected with IL2 or IL4.