Normal mouse spleen, when cultured in vitro for 3 days in the presence of 10(8) heat-killed Listeria monocytogenes organisms, produced colony-stimulating factors (CSF) that were capable of supporting the production of haemopoietic colonies by bone marrow cells in semi-solid agar, or supporting bone marrow proliferation in liquid medium. In contrast, when the spleen cells were prepared from mice that had been infected with Listeria monocytogenes, colony-stimulating activity (CSA) was no longer detectable over a period from Day 3 to Day 17 post-infection. Suppression of CSA was imposed on normal spleen cells when nylon-wool filtered, T-cell enriched spleen cells from infected mice were co-cultured with normal spleen cells. Suppression largely coincided with the production of interferon by whole spleen from infected mice, and when interferon-gamma (IFN-gamma) was neutralized by antibody CSA was again detected. An early IFN-gamma-independent decrease in CSA production was also detected 2-3 days post-infection. The relevance of this system to the control of CSF production in vivo is discussed.