Varieties of Sarcoptes scabiei from different hosts are highly host specific but they are morphologically indistinguishable. The purpose of this study was to investigate the immunologic cross-reactivity among several varieties of scabies mites using serum from a human scabies patient and from several other species of infested hosts. Homologous and heterologous crossed-immunoelectrophoretic (CIE) analysis of extracts prepared from var. canis (dog) and var. suis (pig) mites yielded very similar antigen profiles. Serum from a human patient infested with var. hominis had circulating IgE that bound to antigens present in extracts prepared from each animal mite variety. Antigen homology was further confirmed by fused peaks on tandem CIE. Additionally, sodium dodecyl sulfate polyacrylamide gel electrophoresis/immunoblot analysis showed that the 2 extracts contained proteins that bound antibody in serum from a var. suis-infested pig, a var. canis-infested dog, var. canis-infested rabbits, and a var. hominis-infested human. The results of this study clearly indicate that different varieties of scabies mites, though host specific, introduce some immunologically cross-reactive molecules into the host. However, each serum from the 4 scabies-infested hosts also contained antibody that was specific for proteins in extract from only 1 variety of mite. These data indicated that each variety of scabies introduced some unique molecules into the host, each strain produced some similar molecules, or both, but different hosts responded immunologically to different sets of these.