We have evaluated some of the conditions regulating the selective augmentation of the Ia-positive macrophage population within immunologically induced exudates. Antigen-stimulated T cells secrete a protein referred to as macrophage- (Ia-positive) recruiting factor (MIRF), which when injected i.p. stimulates a 10- to 20-fold increase in the number of Ia-positive exudate macrophages. This response is totally abrogated when mice are lethally irradiated before injection of MIRF or immune T cells. Adoptive transfer of bone marrow cells to irradiated mice substantially restores their ability to respond to the immunologic stimuli, even if the transferred bone marrow has itself been depleted of Ia-positive cells. It was also found that the high level of Ia-positive macrophages induced by MIRF requires a renewable stem cell source in order to be maintained. Finally, even when macrophages were elicited by injecting thioglycollate before irradiation, Ia-positive cells were not induced in response to MIRF. These findings suggest that the target of MIRF in vivo may be restricted to a developmentally young cell within or recently derived from a stem cell compartment such as the bone marrow, and that Ia-positive and Ia-negative macrophages ultimately derive from a potentially common Ia-negative stem cell.