Thermoactinomyces vulgaris, one of the aetiological agents of farmer's lung, was analysed for its ability to activate non-immune spleen lymphocytes from 10- to 14- week-old mice. The lymphocytes were found to exert both enhancing and suppressing signals after activation, depending on the secondary stimulation used. The enhancing effect is due to interleukin-2 secreted mainly by L3T4+ lymphocytes. The suppressive action is associated with Lyt2+ lymphocytes, which are probably activated by prostaglandins or histamine; but the suppression inducer action of L3T4+ lymphocytes may also be important. Genetic regulation, independent of H-2K and D, was also detected between different inbred strains of mice in response to T. vulgaris. The genetic regulation appeared associated with the different responsiveness of Lyt-2 positive lymphocytes between different strains. These results emphasize the importance of nonspecific activation in hypersensitivity disorders induced by microbiol antigens.