Mycobacterium genavense is a recently described microorganism causing disseminated infections in AIDS patients. In this study, we investigate its pathogenicity in mice and some mechanisms of the host response to this bacterium. Following an intravenous challenge of 10(6) organisms, M. genavense grew progressively in the spleens and livers of BALB/c and CBA mice over at least an 8-month period. Granulomas were present in the spleens, livers and lungs of the animals. The numbers of bacteria recovered from the spleens and livers were higher in BALB/c (Bcg(s)) than in CBA (Bcg(r)) mice from day 30. The role of the Bcg gene, in the early phase of infection, was supported by the fact that the bacterial load, on day 15, was higher in BALB/c than in the congenic C.D2 (Bcg(r)) mice. The role of T cells in the host response was suggested by the high susceptibility of nude mice to M. genavense infection. In vivo depletion experiments in CBA mice indicated that gamma interferon and both CD4(+) and CD8(+) T cells participate in the containment of the bacterial load.