In this report, we examine the antigen nonspecific immunoregulating activity of macrophages isolated from the murine methylcholanthrene-induced fibrosarcoma FSA. These cells were shown to enhance the primary anti-CRBC PFC response of whole normal spleen cells in a dose-dependent fashion. This function was associated with a subpopulation of large Ia-negative macrophages and was mediated by a soluble macrophage-derived factor that appeared to act by stimulating the proliferation and/or differentiation of antigen-reactive T cells. The relationship of this factor to previously described monokines is discussed.