Rhodococcal pneumonia is an important, life threatening disease of foals and immunosuppressed humans. Increased knowledge of the mechanisms of protective immunity are required in order to develop an effective immunoprophylaxis strategy for horses and immunotherapeutic regiments for people. Both humoral and cellular components of the immune system may be involved in immune clearance of R. equi. The susceptibility of foals less than 4-6 months of age is postulated to reflect waning maternal antibody, and passive transfer of hyperimmune plasma can provide protection on endemic farms. However, effective clearance is likely to require appropriate cellular responses, including the secretion of cytokines. In murine models, both CD4+ and CD8+ T lymphocytes can reduce bacterial counts in the lung. CD4+ cells appear to be both required and sufficient, and IFN-gamma is a primary mediator. Clearance appears to be a type 1 immune response while type 2 responses may lead to a failure to clear and lesion development. It remains to be determined how the cellular immunity experiments reported in mice relate to horses and humans. Likewise, the role of specific R. equi antigens in protective immunity has not been determined.