Specific pathogen-free B6D2 mice and Hartley guinea pigs were infected subcuta- neously with selected strains of Mycobacterium tuberculosis, M. bovis, M. kansasii, the MAIS complex, M. nonchromogenicum, and M. vaccae, and the in vivo growth behavior of the organisms was correlated with the level of tuberculin hypersensitivity and immunity to tuberculosis that subsequently developed. The peak level of tuberculin hypersensitivity varied depending on the host species, the immunogenicity of the infecting organism, and the dose and route of inoculation. However, the skin or footpad swelling profiles observed in mice and guinea pigs sensitized with live or heat-killed M. tuberculosis (persistor) or M. vaccae (nonpersistor) were very similar when a soluble test antigen was used, peaking between 24 and 36 h and already declining by 48 h. However, if sonically disrupted or whole-cell antigens were used, the swelling response was skewed significantly, with some residual swelling still present at 72 h. However, no evidence for two distinct cellular hypersensitivity responses was obtained in either mice or guinea pigs, regardless of the growth behavior of the mycobacteria in vivo.