Neonatal thymectomy renders animals more susceptible to the carcinogenic action of oncogenic viruses and chemical carcinogens. In man, several thymus-related immunologic deficiency diseases have been shown to be characterized by a markedly increased frequency of malignant tumors as has been chronic immunosuppressive therapy. On the basis of the above and related observations, the recirculating thymic-dependent small lymphocyte has been implicated in the pathogenesis of a variety of spontaneous and artificially induced tumors and it has been postulated that this cell type constitutes an integral part of the immune surveillance mechanism. The remarkable radiosensitivity of the small lymphocyte has been well documented as has been the carcinogenic effect of ionizing radiation. The mechanisms involved in such tumorigenesis are not clear, however, and the relationship between the immunosuppressive effects of exposure to radiation and the neoplastic consequences of such exposure remain poorly defined. The purpose of the present proposal is threefold: 1) to investigate the effect of neonatal and adult thymectomy on the prevalence of spontaneous and radiation-related tumors in germfree and conventional mice; 2) to determine if the tumorigenic effects of radiation can be modified via reconstitution with defined populations of lymphocytes post-exposure; 3) to correlate the above with the immune status of the host, particularly with respect to the number of recirculating thymic-dependent small lymphocytes mobilizable via thoracic duct cannulation. BIBLIOGRAPHIC REFERENCES: Anderson, R.E. and Warner, N.L.: Ionizing radiation and the immune response. Adv. Immunol. 24:215-235, 1976 (in press). Anderson, R.E., Doughty, W.E. and Troup, G.M.: Immunological responsiveness and aging phenomena in germfree mice. In Immunology and Aging (Eds. T. Makinodan and E. Yunis), pp. 151-170, 1976, Plenum Press, New York (in press).