© 2015 Elsevier GmbH. Peromyscus leucopus, the white-footed mouse, is one of the more abundant mammals of North America and is a major reservoir host for at least five tickborne diseases of humans, including Lyme disease and a newly-recognized form of relapsing fever. In comparison to Mus musculus, which is not a natural reservoir for any of these infections, there has been little research on experimental infections in P. leucopus. With the aim of further characterizing the diversity of phenotypes of host responses, we studied a selection of quantitative traits in colony-bred and -reared outbred P. leucopus adults that were uninfected, infected with the relapsing fever agent Borrelia hermsii alone, or infected after immunization with Lyme disease vaccine antigen OspA and keyhole limpet hemocyanin (KLH). The methods included measurements of organ weights, hematocrits, and bleeding times, quantitative PCR for bacterial burdens, and enzyme immunoassays for serum antibodies against both the immunization proteins and cellular antigens of the infecting organism. The results included the following: (i) uninfected animals displayed wide variation in relative sizes of their spleens and in their bleeding times. (ii) In an experiment with matched littermates, no differences were observed between females and males at 7 days of infection in bacterial burdens in blood and spleen, relative spleen size, or antibody responses to the B. hermsii specific-antigen, FbpC. (iii) In studies of larger groups of males or females, the wide variations between bacterial burdens and in relative spleen sizes between individuals was confirmed. (iv) In these separate groups of males and females, all animals showed moderate-to-high levels of antibodies to KLH but wide variation in antibody levels to OspA and to FbpC. The study demonstrated the diversity of host responses to infection and immunization in this species and identified quantitative traits that may be suitable for forward genetics approaches to reservoir-pathogen interactions.