Lyme disease is a common inflammatory disease of North America. It is caused by the spirochetal bacterium Borrelia burgdorferi, which is transmitted by the bite of a small tick, Ixodes dammini. The disease is inconsistent in its manifestation, mimicking a wide variety of maladies, many of which are noninfectious. Currently, there is no practical means for detection of the presence of the organism, and serologic studies offer the best diagnostic aid. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to B burgdorferi antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. Antibiotic therapy early in the infection may interfere with antibody production, but therapy later does not appear to have a significant effect on antibody levels. Because several methods are available for the detection of antibodies and several choices for antibody detected--IgM, IgG, or combinations--the clinical laboratory should provide guidance and advice in choosing and interpreting tests.