Interactions of mouse alveolar macrophages from three different inbred strains of mice and Thermoactinomyces vulgaris, a microbe associated with Farmer's lung disease, were studied. Alveolar macrophages were found to abolish the mitogenic activity of T. vulgaris. A prostaglandin synthesis inhibitor indomethacin, could not restore the activity. Alveolar macrophage supernatants generated by T. vulgaris treatment exerted strong suppression in secondary concanavalin A-induced lymphocyte transformation. Indomethacin partly relieved the suppression but a histamine 2 receptor blocker, cimetidine, had no effect. Interleukin 1 activity was practically undetectable by the thymocyte co-stimulation assay unless indomethacin was used. When indomethacin was used, interleukin 1 activity could be detected in all strains of mice tested. Major differences in the abolition of the mitogenic effect, in the suppressive effect, or in the release of interleukin 1 were not detected between inbred strains of mice tested. The results indicate that alveolar macrophages exert suppressive actions in vitro after T. vulgaris treatment but in vivo activities remain to be elucidated.