Frequencies of IFN gamma- and IL-4-producing spleen cells in response to Mycobacterium bovis BCG infection were determined in C57BL/6 and BALB/c mice. Both mouse strains express equal innate susceptibility to M. bovis BCG (Bcgs), but differ in their NK1.1 and T-cell activities. M. bovis BCG infection induced higher frequencies (f approximately 1/500) of antigen-induced IFN gamma-secreting spleen cells in C57BL/6 mice as compared to BALB/c mice (f approximately 1/8000). Concanavalin A stimulated almost equal numbers of IFN gamma-secreting cells in both mouse strains (f approximately 1/50). Treatment with anti-NK1.1 mAb of M. bovis BCG-infected C57BL/6 mice did not alter frequencies of IFN gamma-secreting cells. Equally low numbers of antigen-induced IL-4-producing cells (f approximately 1/3000) were determined in both C57BL/6 and BALB/c mice during M. bovis BCG infection and treatment of C57BL/6 mice with anti-NK1.1 mAb had no measurable effect on IL-4 producers. Finally, frequencies of IFN gamma-producing cells were markedly reduced (10-fold) in M. bovis BCG-infected TCR-beta-/- gene deletion mutants as compared to their heterozygous controls. Our findings verify that M. bovis BCG infection primarily induces IFN gamma-secreting alpha/beta T cells of TH1 type and show that the frequencies of these IFN gamma producers differ in the two Bcgs mouse strains C57BL/6 and BALB/c.