Stimulation of cultures of murine bone-marrow cells with specific macrophage growth factor (colony-stimulating factor I) resulted in the production of type I interferon. Neutralization of this endogenous interferon by antiserum directed against interferons alpha and beta resulted in a significant enhancement of mononuclear phagocyte proliferation from committed marrow precursors. The effect of the antiserum was lost in cultures depleted of adherent cells, an indication that an adherent regulatory cell (or cells) in the marrow limits mononuclear phagocyte proliferation by producing antiproliferative interferon in response to high levels of specific growth factor.