The cell-mediated immune response of cattle to Mycoplasma mycoides var. mycoides was studied. Sensitized lymphocytes in blood leukocyte preparations showed a significant degree of antigen-induced transformation, judged by the uptake of tritiated thymidine. The increase in tritiated thymidine uptake in sensitized lymphocytes in the presence of M. mycoides membrane antigen varied from 2- to 13-fold compared with the controls, and this increase in activity was observed from 3 days after artificial infection. Inhibition of leukocyte migration by M. mycoides membrane antigen commenced between 17 and 30 days after infection, and preliminary observations indicate that this test correlated with the intradermal allergic test. M. mycoides-induced unresponsiveness was demonstrated 23 and 30 days after infection. Unresponsiveness, in that the lymphocytes did not respond to phytohemagglutinin, was very marked in two of three animals and partial in the third animal, whereas the humoral antibody response did not appear to be affected. Antigen-induced transformation was demonstrated in only two out of six cattle vaccinated two months previously with M. mycoides T(1) broth culture vaccine, and óne animal only gave a doubtful intradermal allergic reaction. A further six cattle vaccinated 15 months previously were negative to both the leukocyte migration inhibition test and the intradermal allergic test.