Conventional CBA mice subjected to lethal whole-body irradiation and allogeneic bone-marrow transplantation developed delayed secondary disease, which caused 95% mortality within 100 days. Symptoms of secondary disease as well as mortality were virtually absent in similarly treated mice kept in the germfree state or given a colonization-resistant (CR) flora. Conventionalization of these mice as early as 40 days after transplantation did not induce a significant degree of secondary disease except in 1 group of CR mice derived from conventional mice by antibiotic treatment. The acute form of secondary disease occurring after transplantation of allogeneic spleen cells was much less influenced by the gnotobiotic conditions, which confirmed the concept that the mortality was caused primarily by severe graft-versus-host reactions. The implications of these findings for the treatment of patients receiving bone-marrow grafts are discussed.