The intracellular growth kinetics of Mycobacterium avium and H37Rv (virulent) and H37Ra (avirulent) strains of Mycobacterium tuberculosis were compared by use of both the professional (mouse bone marrow-derived macrophages, BMMO) and nonprofessional (mouse L-929 fibroblast cell line) phagocytes. The results obtained showed that all the mycobacterial strains grew more actively in fibroblasts than in BMMO. This difference was paralleled by lesser acid phosphatase (AcP) labeling of noninfected fibroblasts and the observation that upon infection both the proportion of AcP-positive cells and AcP content were higher in BMMO than in L-cells during the 7 days of infection. In parallel experiments, intracellular growth of M. tuberculosis H37Rv and M. avium was compared inside BMMO from both the Bcg(s) (C57BL/6) and BCg(r) (DBA-2) mice, which were matured and differentiated with either an L-cell-conditioned medium (LCM) obtained from control, noninfected L-929 cells, or a LCM obtained with M. tuberculosis- or M. avium-infected L-cells. Upon mycobacterial infection, fibroblasts were able to secrete mediators that stimulated the BMMO to better control the infection by pathogenic mycobacteria. These results are discussed in terms of the mycobacteria-fibroblast interactions and their eventual role in the immune modulation of the host's response to invading mycobacteria.