The establishment of cancer in a host involves at least two major events: the escape of tumor cells from normal growth control and their escape from immunological recognition. Because of this nature of their development, cancer cells seem to be predominatly poorly immunogenic. In contrast to the previous idea that cancer cells express no recognizable antigens, recent progress in the identification and characterization of tumor antigens, as well as the expansion of knowledge on the cellular and molecular mechanisms of antigen recognition by the immune system, have raised the possibility of using immunotherapy to treat certain tumors. Information on these mechanisms has been obtained in three crucial areas: 1) the role of cytokines in the regulation of the immune response, 2) the molecular characterization of tumor antigens in both mouse and human tumors, and 3) the molecular mechanisms of T cell activation and antigen presentation. Such information has provided new insight into tumor immunology and immunotherapy. Furthermore, recombinant DNA technology allows for modification of the genome of mammalian cells for therapeutic purposes in several diseases. Several novel strategies have been developed to derive genetically modified tumor cells and use them as cellular vaccines to induce antitumor immunity in animal tumor models. This combined modality of genetically modified tumor cells and immunotherapy has been termed immunogene therapy of tumors. Crucial to this approach has been the ability to transfer into normal or neoplastic cells genes known to increase the immunogenicity of cells, which subsequently can be used to augment immune reactions in tumor-bearing mice or cancer patients. While there has been success in inducing antitumor immunity in some tumor models, there are difficulties and limitations in the application of these gene-modified tumor cells for the treatment of preexisting tumors. In this review, recent progress in cancer immunogene therapy is discussed.