The DNA synthesis in syngeneie, allogeneic and xenogeneic cells was inhibited by peritoneal macrophages of normal WKA rats. This inhibitory effect of macro phages was found to be mediated by a soluble factor (MfID) released into a culture medium from macrophages which was heat-stable and non-dialyzable. The MfID was also responsible for the inhibition of lymphocyte DNA synthesis by MIX reaction.The action of MfID was indicated to suppress rather than to kill cell growth.It was interpreted that the inhibitory effect of macrophages on cellular DNA synthesis is their inherent property and macrophages may play the role of regulating the proliferation of lymphocytes and other cells. rat peritoneal macrophage; macrophage soluble factor; DNA synthesisIt is well known that macrophages are essential cells at the site of inflamma tion, wound repair, graft rejection, etc. However, the role of macrophages in these areas has not been well defined. Recently, macrophages have been shown to inhibit DNA synthesis in lymphocytes (Harris