Swine infected with Mycobacterium bovis and Mycobacterium avium were studied for development and specificity of lymphocyte immunostimulation and tuberculin skin reactivity to purified protein derivatives (PPD) of tuberculins. Lymphocytes from infected animals had maximal blastogenic responses to PPD prepared from the homologous organisms. The time of appearance of specifically sensitized lymphocytes was studied, as was the specificity of skin reactivity. In vitro lymphocyte responses of M avium serotype 1-infected swine to M avium serotype 1 PPD were greater than were the responses of M avium serotype 2-infected swine to the same antigen. Results indicate that the specific stimulation of sensitized lymphocytes might prove useful in the diagnosis of tuberculosis in swine and in differentiating infections due to different serotypes of M avium.