Babesia microti and Borrelia burgdorferi, the spirochetal agent of Lyme disease, are both transmitted by the tick Ixodes dammini. Serological evidence has shown that 54% of the patients with babesiosis tested have IgG and IgM antibodies to the spirochete causing Lyme disease. Likewise, 66% of randomly selected patients with Lyme disease from geographic areas endemic for both diseases, but not from areas where babesiosis does not occur, also have IgM and IgG antibodies to B. microti. Antigenic cross-reactivity is not the reason for these findings, as laboratory animals experimentally infected with B. microti do not develop antibodies to B. burgdorferi, and laboratory animals immunized with organisms derived from pure cultures of spirochetes do not develop antibodies to B. microti. We suggest that these patients are concurrently exposed to both organisms by doubly infected tick vectors.