B6C3F1 mice that had been thymectomized at 8 to 12 weeks of age, subjected to 950 R of whole-body X irradiation, and transfused with syngeneic bone marrow were challenged in a footpad with Mycobacterium leprae or M. marinum, or intravenously or intraperitioneally with Listeria monocytogenes. Also, mice inoculated with M. leprae in a hind footpad were administered dapsone in the mouse chow. The thymectomized-irradiated (T + R) mice did not survive as well as non-thymectomized mice when housed in the vivarium with no special precautions, but survived sufficiently well to permit the completion of some long-term experiments. M. leprae multiplied to a higher "ceiling" and survived longer in the T + R mice than in the non-thymectomized controls. But a ceiling to multiplication of M. leprae was imposed, and finally the organisms were killed. The histopathological appearance of the footpad tissues, studied by electron microscopy, was consistent with the measurements of bacterial numbers and viability. Swelling of the footpad after local inoculation with M. marinum was greater in T + R mice than in non-thymectomized controls. Similarly, the number of L. monocytogenes following intravenous challenge was greater in the spleens of T + R than of non-thymectomized mice, and the survival of the T + R mice was impaired after intraperitoneal challenge with L.monocytogenes, compared to the survival of non-thymectomized mice. None of these differences was striking, suggesting that these T + R mice had retained or regained some immune competence. The effects of dapsone treatment of T + R mice inoculated with M. leprae were much the same as those of treatment of non-thymectomized mice. Because these T + R mice were not greatly immunosuppressed, they would not have provided a model of human lepromatous leprosy suitable for chemotherapeutic studies.