The studies described in this paper provide evidence that the pathogenesis of Salmonella typhimurium in mice is dependent on interactions between particular genotypes of the infected mice and the infecting Salmonella strain. This conclusion was based on data obtained by infecting a panel of BXD recombinant inbred mice with each of three S. typhimurium strains. One of the S. typhimurium strains was a transconjugant (WB500) produced in an interrupted mating between the two other strains, one (SR-11) of high and the other (LT2-Z) of low virulence for BALB/c mice. We found that strain WB500 appeared to have inherited from SR-11 a gene (or genes) which was required to exploit the Itys/s genotype in mice. However, WB500 apparently lacked other SR-11 virulence gene(s), whose effect on the in vivo growth of SR-11 was independent of the Ity genotype of the mouse.