Although the dissemination of tuberculosis is aerogenic, less than 10% of infected subjects develop the active disease. Local immunity plays a major role in systemic cell-mediated immunity against this disease. BCG immunization may be more effective if administered via aerosol rather than intradermally. In this study, the immune responses seen in guinea-pigs vaccinated with a BCG aerosol were compared with those seen following intradermal vaccination. At regular intervals after each vaccination, the activation of alveolar macrophage was determined by their capacity to produce superoxides, phagosome-lysosome fusion and the inhibition of in vitro BCG growth. Concurrently, BCG multiplication or growth inhibition in the target organs was also determined. This study demonstrates that the alveolar route of BCG administration activated broncho-alveolar macrophage more effectively than the intradermal route. Superoxide production correlated with in vitro and in vivo inhibition of BCG growth. The spread, by the BCG inoculum, to the draining lymph nodes and spleen was similar for both test routes of administration. However, the lung BCG counts were significantly lower following intradermal vaccination. In contrast, the activation of broncho-alveolar macrophage was higher following aerogenic, rather than intradermal, BCG immunization.