Several species of the genus Borrelia exhibit antigenic variation of variable major proteins on their surface during relapsing fever. We have investigated the African relapsing fever species Borrelia crocidurae during infections in mice and compared it with the thoroughly studied North American species Borrelia hermsii. A major difference between the two species is that B. crocidurae can bind and become completely covered with erythrocytes. In addition, B. crocidurae causes a prolonged spirochetemia which coincides with a delayed appearance of antiborrelial antibodies. We show that the antibody response against an unrelated antigen is not delayed and that antibiotic treatment, which dissociates rosettes and inhibits the spirochetes, also leads to an early antibody response. Taken together, the erythrocyte aggregation and prolonged spirochetemia hint at a new mode of immune evasion where erythrocyte-covered spirochetes may avoid contact with the phagocytic cells and B cells of the immune system, thereby delaying the onset of a specific immune response.