The screening of the cytokines that are involved in the control of mycobacterial infections in vivo may be used to select candidates for immunotherapeutical trials. We looked at the in vivo expression of different cytokines during Mycobacterium avium infection of mice and found a correlation between resistance and the level of expression of IFN-gamma and TNF-alpha. The use of specific neutralizing antibodies in vivo led to the identification of IFN-gamma and TNF-alpha as protective cytokines acting at the effector level of resistance to M. avium and M. tuberculosis. Furthermore, we found that IL-6 was involved in the induction of protective T cells in M. avium infections and that it was necessary to maintain sterilizing immunity in mice infected with M. tuberculosis. Regarding the antimycobacterial mechanisms of the macrophage against M. avium we found no role for oxygen or nitrogen reactive intermediates but rather the involvement of phagosomal acidification.