An infection model of human tuberculosis was established with C57BL/6J mice. The lymphocyte proliferative responses to antigens from Mycobacterium tuberculosis were investigated during the course of infection and compared with results obtained with a group of mice immunized with large amounts of killed bacteria. The two groups responded similarly to a number of mycobacterial antigens, but marked differences in responses against secreted antigens were found; only infected mice responded vigorously to these. The responding lymphocyte subpopulation was made up of L3T4+ T lymphocytes under restriction of the Ia molecule.