Organisms belonging to the Mycobacterium avium complex are the most common bacteria isolated from patients with AIDS. In these patients, M. avium is associated with disseminated disease, and bacteria are found within macrophages in the liver and spleen. To examine the potential of M. avium infection of a nonprofessional phagocyte, the murine fibroblast cell line (L929 cells) are infected with strain 101 (serotype 1) of M. avium. The duplication time for the intracellular bacteria was approximately 36 hr. Progressive intracellular growth ultimately resulted in the destruction of infected cells (after approximately 12 days in culture). Supernatant obtained from infected L929 cells contained interferon-beta (IFN beta) and granulocyte macrophage colony stimulating factor (GM-CSF) (50 +/- 12 ng/10(5) cells and 63 +/- 18 pg/10(5) cells, respectively, by 18 hr). IFN beta could be detected by 3 hr after infection, while GM-CSF was first detected by 6 hr. Release of IFN beta by infected L929 cells could subsequently stimulate NK cells, but not macrophages, to lyse infected L929 cells. These data using L929 cells suggest that M. avium may invade fibroblasts during the course of the infection and that fibroblast infection may trigger NK cell-mediated cytotoxicity against the infected fibroblasts.