Positive skin reactions to homologous antigens in mice infected with Mycobacterium leprae were observed at the time that the bacillary multiplication was nearing the plateua level. Once developed, the skin reactivity persisted for a considerable length of time. Lymphocyte transformation studies indicated that the lymphocytes from infected animals were unable to respond to specific antigenic stimuli in the early phase of infection. Possible explanation for this failure could be that the lymphocytes although sensitized, were not capable of responding to the stimuli due to a rather low level of sensitization. The elevated lymphocyte stimulation index in the later stages of infection, coupled with skin reactivity indicates the production and proliferation of antigen-reactive lymphocytes which in turn govern the activity of mononuclear phagocytic cells through the production of lymphokines. Occurrence of all the events appears to coincide with the time closer to the plateauing of M. leprae in the foot pad of the mouse. It is suggested that the cell-mediated immune response in the M. leprae infected mouse is basically a T cell rather than a B cell response.