Experiments were performed to elucidate the role of colony-stimulating factors in host defenses to the intracellular pathogen Listeria monocytogenes. Mice were protected against Listeria sp. by adoptive transfer of immune spleen cells and were then challenged with listeriae intravenously. Control mice were injected with spleen cells from uninfected mice. Adoptively immunized (immune) mice had significantly fewer listeriae in spleens and livers 2 and 4 days after Listeria challenge than did control mice. During acute infection, colony-stimulating activity in serum was increased earlier (10 h) in immune mice than in controls. Concentrations of colony-stimulating activity were equal at 24 h. By 48 h, values were decreased in immune mice, but were elevated in control mice. Similar changes were noted when a specific colony-stimulating factor, macrophage colony-stimulating factor, was measured in serum by using a radioimmunoassay. The changes in serum colony-stimulating activity in mice adoptively immunized with immune spleen cells were eliminated if spleen cells were first treated with anti-Thy-1.2 monoclonal antibodies. The number of macrophage progenitor cells in bone marrow and spleen were also determined as measures of the hemopoietic potential in these organs. The number of macrophage progenitor cells in bone marrow was higher in immune animals than control animals at 1, 2, and 4 days of infection. Similarly, the number of these cells in spleens was higher during the early stages of infection in immune mice. These results indicate that both the regulation of leukocyte production and the transfer of specific cellular immunity by spleen cells are associated, and they therefore suggest that hemopoietic regulatory factors play a role in immune host defenses.