A killed, armadillo-derived Mycobacterium leprae vaccine was examined for its ability to induce cell-mediated responsiveness in purified protein derivative (PPD)-positive volunteers residing in a nonendemic country using the lymphocyte transformation test (LTT). A marked increase in the proliferative responses to a M. leprae-soluble antigen preparation was observed in the two groups which were vaccinated with the highest doses of the vaccine, i.e., 1.5 X 10(8) and 5 X 10(8) bacilli. This increase was observed in both groups 3 months after vaccination, and persisted for the study period of 1 year. The in vitro proliferative responses to whole bacilli, of both armadillo and human origin, showed a similar but smaller increase 3 months after vaccination. Some enhancement of responses to cross-reactive antigens, such as PPD, and to unrelated antigens such as streptokinase-streptodornase, tetanus toxoid and diphtheria toxoid, was also observed. Thus, the LTT revealed that while the killed M. leprae vaccine induced a specific cell-mediated response to M. leprae, it was also responsible for a nonspecific immune-enhancement effect in healthy volunteers.