Lyme disease is an inflammatory disorder of skin, joints, nervous system, and heart. The disease is associated with a preceding tick bite and is ameliorated by penicillin treatment. A spirochete (IDS) isolated from Ixodes dammini ticks has been implicated as the etiologic agent of Lyme disease. We examined the antibody responses of Lyme disease patients to IDS lysate components in order to further understand the pathogenesis of this disease. The components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, reacted with patients' sera, and the bound IgG was detected with 125I-labeled protein A (western blot). We found that (a) Lyme disease patients had antibodies to IDS components (b) most patients studied had antibodies to two components with apparent subunit molecular weights of 41,000 and 60,000, and (c) the patients' antibody responses during illness and remission were specific, for the most part, for the IDS. In contrast to the findings with Lyme disease sera, sera from controls showed little reactivity with IDS components in either the western blots or a derivative solid-phase radioimmunoassay.