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When irradiated hamsters are passively immunized with immune serum before challenge with Borrelia burgdorferi, they are completely protected from arthritis and infection. The complement dependency of this protection was addressed by treating hamsters with cobra venom factor. Depletion of complement abrogated the ability of immune serum obtained 1 and 10 weeks after infection to confer complete protection. By contrast, depletion of complement had no effect on the ability of 3-week immune serum to confer protection. These results suggest that complement-dependent, and possibly complement-independent, antibodies are important for preventing the induction of Lyme arthritis.