Guinea pigs infected by the respiratory route with small numbers of Mycobacterium tuberculosis, strain H37Rv or strain H37Ra, or with Mycobacterium smegmatis were sacrificed at weekly intervals after infection, and the number of mycobacteria recoverable from the lung, bronchotracheal lymph node, and spleen was determined. Strain H37Ra increased 1,000-fold in the lung during the first 3 weeks of infection; then, after a short stationary phase, the organisms were eliminated from the lung by the twelfth week. Strain H37Rv increased somewhat more rapidly in the lung, achieving a stationary level 100-fold greater than that for H37Ra. in contrast to the fate of H37Ra, this stationary high level of H37Rv was maintained to the termination of the experiment, 18 weeks after infection. Both H37Ra and H37Rv were recovered from the lymph nodes and spleen. Mycobacterium smegmatis failed to multiply in the lungs of guinea pigs that had inhaled and retained approximately 2,000 viable bacilli.