Macrophage Inhibitory Factor - A3 (MIF-A3), a glycolipid compound derived from Mycobacterium avium serovar 2, has previously been shown to inhibit the candidacidal activity of activated bovine peripheral blood-derived macrophages (MF). This compound appears to be a potent scavenger of reactive oxygen species in zymosan stimulated sheep alveolar macrophages and in a cell-free system. It does not affect phagocytosis of sheep alveolar MF and has no effect on nitric oxide production of g-interferon stimulated murine C57BL/6 thioglycolate-elicited peritoneal-derived MF. In this study, a similar inhibition of candidacidal activity was detected in MIF-A3 treated thioglycolate-elicited murine C57BL/6, C57BL/10, C3H/HeJ and A/J MF. Inhibition of candidacidal activity was demonstrated at MIF-A3 concentrations ranging from 100-400 mg/ml in MF without additional stimulators (exception C3H/HeJ) and in MF additionally stimulated with 200 U/ml g-interferon, 100 ng/ml phorbol myristate acetate (PMA) and 0.4 ng/ml E. coli lipopolysaccharide (LPS) from all mouse strains tested (C57BL/6, C57BL/10, C3H/HeJ and A/J). The decreased candidacidal effect produced by MIF-A3 was dose-dependent and appeared greatest in PMA and LPS treated MF. This effect could be neutralized by the addition of goat anti-MIF-A3 antiserum. Differences in the response to treatment with MIF-A3 of MF from different mouse strains were present and show that MF from the Bcgs mouse strains (C57BL/6 and C57BL/10) are significantly more sensitive to the effect(s) of MIF-A3 than the Bcgr mouse strains (C3H/HeJ and A/J).