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Mycobacterial infections in mice are normally characterized by a profound Th1 cell-mediated immune response, in which T cells secrete large amounts of IFN-gamma. Recent evidence suggests that this response also includes a Th2 component. In order to investigate whether production of IL-4, IL-5, or IL-10 influenced the outcome of a Mycobacterium bovis-bacille Calmette-Guérin (BCG) infection, we intranasally infected IL-4, IL-5, and IL-10 gene-deficient and control mice and monitored the resulting immune response and bacterial clearance. IL-4, IL-5, and IL-10 deficient mice cleared the mycobacteria with the same kinetics as control mice. Furthermore, T cells of cytokine deficient and control mice produced similar levels of IFN-gamma following in vitro stimulation with purified protein derivative (PPD) from M. bovis. We conclude that the cytokines IL-4, IL-5 and IL-10 are not essential for and do not negatively influence the protective immune response against M. bovis-BCG in the lung of mice.