Panels of congenic mouse strains that differ by the alleles of a certain chromosomal segment and by the level of susceptibility to tuberculosis (TB) infection is a precise tool for adequate dissection of host TB genetics, immunology and pathology, as well as the efficacy of TB-vaccines and drugs. Here we present two H2-congenic strains on the C3H genetic background, C3H.JK (H2j) and C3H/HeDiSn (H2k) which differ profoundly in TB susceptibility, and a new I.B6 panel of H2-congenic strains on the well-characterized TB-susceptible I/St H2j genetic background. H2j haplotype determines a high level of TB susceptibility. After inoculation with a high dose of Mtb, I/St, C3H/HeDiSn and C3H.JK mice displayed similar mortality curves. Gradual dose reduction, leading to less severe TB manifestations, allowed identification the C3H/HeDiSn strain as the most TB-susceptible in terms of survival time, lung CFU counts and lung pathology. For further studying the role of the H2 and background genes in TB control, we now perform segregation genetic analysis (F2 dissection) of relevant phenotypes.