Studies of various mouse strains in the C3H lineage have shown that there is no correlation between innate susceptibility to Salmonella infection and sensitivity to the toxic or mitogenic effects of lipopolysaccharide (LPS). C3H/HeNCrlBR mice were Salmonella resistant, but sensitive to the toxic and mitogenic effects of LPS, whereas C3HeB/FeJ mice were Salmonella susceptible as the C3H/HeJ mice, yet were mitogenically responsive to LPS and sensitive to its lethal effects. Furthermore, other mouse strains (C3H/HeTex and C3H/HeDub) displayed intermediate susceptibility to Salmonella infection and were responders to the mitogenic and toxic effects of LPS. These results are interpreted to mean that endotoxemia cannot be a major factor in the pathogenesis of Salmonella infection and provide evidence for the involvement of multiple factors in the control of innate resistance to Salmonella infection in mice of the C3H lineage