The sensitivity of Borrelia burgdorferi sensu lato to animal sera was analyzed. Complement-mediated borreliacidal effects were observed with particular combinations of host serum and Borrelia genospecies. The species-specific pattern of viability and/or lysis is highly consistent with the pattern of reservoir competence of hosts for B. burgdorferi sensu lato, suggesting a key role of complement in the global ecology of Lyme borreliosis.