We demonstrate that 2-month-old female B10.T(6R) mice are highly resistant to systemic infection with the KIM5 strain of Yersinia pestis and that B10.T(6R) mice become susceptible to Y. pestis infection by the age of 5 months. In this study, young (2-month-old) and middle-aged (5- to 12-month-old) B10.T(6R) mice were infected with equal CFU counts of Y. pestis. The 50% lethal dose (LD(50)) for young B10.T(6R) mice was ∼1.4 × 10(4) CFU, while middle-aged B10.T(6R) mice exhibited an LD(50) of ∼60 CFU. Elevated bacterial burdens were found in the spleens of middle-aged mice at 24 and 60 h and in the livers at 60 h postinfection. Immune cell infiltration was greater in the livers of resistant young mice than in those of middle-aged mice and mice of the susceptible C57BL/6N strain. Unlike susceptible mice, young B10.T(6R) mice did not develop necrotic lesions throughout the liver. Instead, livers from young B10.T(6R) mice contained granuloma-like structures. Immunohistochemical staining of liver sections from these mice at 60 h postinfection revealed that the majority of immune cells present in these structures were neutrophils. These findings suggest that resistance to plague in B10.T(6R) mice correlates with early formation of neutrophilic lesions in the liver.