Previously, it was shown that macrophages isolated from liver granulomas of Schistosoma mansoni-infected mice constituted about 30% of the granuloma cell population, were highly activated, and more than 50% displayed H-2 I region-associated antigens. Moreover, the degree of macrophage maturation/activation correlated with the intensity of the granulomatous response. Thus, inflammatory macrophages from the vigorous granulomas of acutely infected mice (VigGrM phi) displayed greater phagocytic and tumoricidal activity than did M phi from the T suppressor cell-modulated granulomas (ModGrM phi) of chronically infected animals. No difference was seen, however, in the percentage of Ia-bearing M phi isolated from vigorous or modulated liver granulomas. Presently, accessory activity of GrM phi was assayed by reconstitution of the proliferative responses of M phi-depleted lymphocytes. Both VigGrM phi and ModGrM phi were able to reconstitute the Con-A induced proliferation of normal thymoctyes. Moreover, both types of GrM phi could reconstitute parasite egg antigen-specific proliferation of the mesenteric lymph node cells from acutely infected mice. Reconstitution was dependent on M phi that displayed I-A and I-E subregion-encoded determinants. In higher doses the activated VigGrM phi were more suppressive toward lymphocytic proliferation than were the less activated ModGrM phi. Apparently, the degree of M phi suppressor activity was in direct relationship to the state of M phi maturation/activation. These data indicate that the inflammatory M phi of the schistosome granuloma may be involved in the focal immune accessory/regulatory events that occur within these T cell-mediated lesions.