Hypergammaglobulinemia is a frequent complication of tuberculosis. Serum levels of each class of immunoglobulin were analyzed among tuberculosis patients. Adult patients had high levels of IgG and IgA, but IgM levels were not elevated. These data suggested that antibody responses to mycobacterial antigens might be influenced by individual immune responses. In order to analyze the specific antibody responses to mycobacterial antigens, IgG class antibodies reactive with BCG proteins were enumerated by an enzyme-linked immunosorbent assay (ELISA). Patients were shown to have significantly higher a mount of IgG antibodies than healthy controls. Sera from patients with active tuberculosis had high consistently titers of antibodies. Antibody titers returned to a normal range after effective treatment, suggesting that the measurement of IgG anti-BCG antibodies would be useful for the diagnosis and follow-up of tuberculosis. In addition, serum antibody profiles were analyzed by immunoblotting. Sonicated whole BCG proteins were electrophorased and transferred to nylon sheets by Western blotting. Then the sheets were developed with sera from patients or controls. Mycobacterial cell wall contains a vast array of proteins so that comparison of the antibody profiles from different sera revealed striking individual variations. However two kinds of proteins, whose molecular sizes were 65KDa and 16KDa, were considered to be significant. The 65 KDa protein was recognized in most sera from both patients and controls. The protein may be related to a "common antigen" present in a wide variety of bacteria. These observations may shed a new light on the role of 65KDa protein in the regulation of the immune systems, for example a individual highly primed to 65KDa protein may amount an exaggerated and potentially harmful response to cross-reactive antigens from other essentially non-pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)