The induction of mucosal immune responses is particularly important for protection against diseases for which entry and pathogenesis are clearly related to the mucosal system, such as salmonellosis, AIDS or tuberculosis. We investigated the immune responses in guinea-pigs vaccinated by BCG via the respiratory compared to the intradermal route. The results demonstrate that the aerogenic BCG induced a better activation of broncho-alveolar macrophages and a substantially improved protective effect against a virulent challenge with Mycobacterium tuberculosis. We also use a DNA recombinant BCG expressing LacZ gene to investigate the influence of various routes of administration on the immunogenicity of the β-galactosidase, a foreign antigen expressed by the LacZ-BCG recombinant. Thus, lymph-node proliferative responses, delayed type hypersensitivity and antibody responses specific for β-galactosidase can be produced in guinea-pigs immunized orally, respiratorily and intradermally. The respiratory and especially the oral route of administration produced higher mucosal and systemic immune responses compared with the intradermal route of immunization. Moreover, the oral immunization of mice with recombinant BCG induced IgA responses which can be detected both in sera and in intestinal secretions. In conclusion, BCG recombinants may be of potential use as an adjuvant vaccine.