Scabies is an important parasitic disease that continues to persist throughout the world despite the availability of acaricides to control it. The immune response mechanism to scabies and the possible development of a vaccine for control of scabies was investigated. This study demonstrated that hosts infested with scabies develop immunity (resistance) to reinfestation. All hosts developed scabies-specific elevated circulating antibody titers during scabies infestations that followed the classical pattern for primary and secondary infestations. Parallel elevated levels of complement C3 were also observed. The hosts that exhibited acquired immunity after their first infestations had antibody and complement levels during challenge infestations lower than those of the hosts that showed no immunity when reinfested. Induction of immunity coupled with generally elevated antibody levels for both immune and nonimmune hosts suggested that resistance to reinfestation was associated with a cell-mediated response. These data also suggested that vaccination with specific scabies tissue containing the relevant antigens or recombinant relevant antigens could enhance the cell-mediated response to protect the hosts against natural infestations.