Background. The antitumor effects of three mouse mammary tumors transfected to express interferon-γ were evaluated. Methods. Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected with highly efficient viral vectors. Wild type or transfected tumor cells were injected subcutaneously into Balb/c mice. Animals were observed for tumor growth and the induction of immunologic memory. Results. A significant decrease occurred in the size of all transfected tumors, EMT6 1.9cm2, DA3 1.7, and 410 1.8 compared with nontransfected control tumors with a mean size of 4 cm2 on day 30. To further test the development of immunity, animals were injected with either nontransfected or transfected tumors and challenged with nontransfected tumor. Animals immunized with transfected tumor cells had significantly smaller tumors, EMT6 2.5 cm2, DA3 3.1, and 410 2.4 compared with controls with a mean size of 4 cm2. No specific splenocyte cytotoxicity was shown. Expression of major histocompatibility complex class I antigens was enhanced in the 410 and DA3 tumor lines. Conclusions. Significant antitumor effects were observed after interferon-γ gene transfection of three mouse mammary cancer cell lines. Up-regulation of major histocompatibility complex class I antigen expression is a partial explanation of these findings. These results provide preliminary studies for gene therapy of human breast cancer.