Six common inbred strains of mice and their F₁ hybrids were examined for resistance to infection with the H37Rv strain of Mycobacterium tuberculosis. According to survival times after inoculation of 10⁵ CFU intravenously (i.v.), the mice could be classified as being either highly susceptible (CBA, DBA/2, C3H, 129/SvJ) or highly resistant (BALB/c and C57BL/6). F₁ hybrids of susceptible and resistant strains were resistant. Although an examination of a limited number of H‐2 congenic strains showed that the H‐2^k haplotype could confer susceptibility on a resistant strain, it was evident that non‐major histocompatibility complex (MHC) genes were much more important. Resistant strains all possessed the susceptibility allele of the anti‐microbial resistance gene, Nramp1. Results obtained with selected strains infected with 10² CFU of M. tuberculosis by aerosol agreed with the results obtained with mice infected i.v. The size of the bacterial inoculum was important in distinguishing between resistant and susceptible strains, in that a 10⁷ inoculum overcame the resistance advantage of one strain over another.