IL-6 was transiently expressed in sera of mice after a bolus intravenous injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF at 250 micrograms/kg/day for 5 days prior to an injection of 25 micrograms/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor cells 7-fold when injected intravenously. Spleen macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS-stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously administered M-CSF was detected at higher concentration and for longer duration in the spleen than in any other organs examined. Spleen macrophages incubated in-vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced IL-6 than untreated cells. These results indicate that intravenously administered M-CSF not only enhances macrophage development in the spleen, but also primes mature macrophages for cytokine production.