The frequent failure of the host's immunologic responses to impose restraints on tumor growth and dissemination has led to the realization that a number of factors, both immunologic and nonimmunologic, may act in concert to affect tumorigenesis. Immunologic mechanisms involved in tumor cell destruction are predicated principally on in vitro procedures, but the relevancy of these experimental observations to the actual events in vivo remains unclear and unresolved. The macrophage has been shown to be an integral segment of the immune response and to constitute an important element of the host defense against tumors. In this connection, interferon may be implicated in tumor cell destruction through macrophage activation to cytotoxicity. Studies of age-related susceptibility of New Zealand Black mice to three different carcinogens, ie, 3-methylcholanthrene, x-irradiation, and murine leukemia virus, have further emphasized the multifactorial determinants which may be operational in oncogenesis. Advances in our knowledge of tumor immunology have suggested a number of possible modalities for preventing tumors from escaping immunologic destruction and should continue to contribute to further elucidation of neoplastic mechanisms.