The susceptibility of laboratory mice to Borrelia burgdorferi was evaluated for selected genotypes and ages. C3H/He, SWR, C57BL/6, SJL, and BALB/c mice inoculated at age 3 days developed uniformly severe polyarthritis at 30 days after intraperitoneal inoculation. Mice inoculated at age 3 weeks also developed polyarthritis, but severity was influenced by genotype, with C3H/He and SWR mice the most severely affected. Susceptible strains developed higher IgG ELISA antibody titers to B. burgdorferi than did resistant mice. Adult (12 weeks) C3H/He mice were also susceptible, but arthritis was not as severe as in those inoculated at age 3 weeks. SKH (hairless) mice developed polyarthritis but not skin disease when inoculated intradermally. Carditis occurred frequently among C3H/He, BALB/c, and hairless mice and in some SWR mice but not in C57BL/6 or SJL mice. This study demonstrates that severity of Lyme borreliosis is age- and genotype-dependent and that laboratory mice are a potentially valuable model.