One week old LEW/N rats were inoculated with 15 different isolates of Borrelia burgdorferi from 3 major North American (Northeast, Midwest, and Pacific) and 1 European endemic areas. At 30 days after inoculation, several tissues were cultured for B. burgdorferi and examined for histopathological changes. Sera were tested for IgM and IgG antibody to B. burgdorferi by an enzyme-linked immunosorbent assay. One or more isolates from each geographic region was recovered by culture and caused arthritis in the rats. No differences in pattern or severity of disease were apparent among pathogenic isolates. Several recovered isolates failed to infect rats, or did not cause disease. Rats that were actively infected seroconverted but uninfected rats did not. Infectivity and pathogenicity of B. burgdorferi isolates could not be correlated with molecular weights or expression of outer surface proteins based on agar gel electrophoresis.