Actinomyces viscosus, a normal inhabitant of the oral cavity, has previously been shown to evoke immune responses in the host. Macrophage activation by this microorganism was studied in a murine system. Peritoneal macrophages, activated in vivo by A. viscosus had a suppressive effect on lymphocyte proliferation in vitro; total suppression occurred at a PEC to lymphocyte ratio of 6:10. A. viscosus‐activated macrophages also suppressed the proliferation of normal syngeneic fibroblasts, with a 96% suppression at a PEC to fibroblast ratio of 9:1. Resident peritoneal macrophages had no suppressive effect on either target cell population. Suppression of fibroblast proliferation by A. viscosus‐activated macrophages was partially reversed by catalase (20000 U/ml) or indomethacin (10‐5M), suggesting involvement of hydrogen peroxide and cylo‐oxygenase product(s). A. viscosus‐activated macrophages produced, upon stimulation, large amounts of H2O2 (256 nmole per mg protein, in 120 min) which were comparable to those produced by C. parvum‐activated macrophages. Resident peritoneal macrophages produced only minor quantities of H2O2 under the same conditions. The suppressive effects observed suggest that A. viscosus, by activating macrophages, may modulate the host's immune response and may hamper the repair potential of chronically inflamed connective tissue by inhibition of fibroblast proliferation. Other constitutents of the plaque may share this effect.