Mycobacterium tuberculosis-specific antibodies (immunoglobulin M [IgM], IgE, IgG, and IgG subclasses) were determined in 164 tuberculosis patients (pulmonary involvement, n = 135; lymph node involvement, n = 29), 59 healthy household contacts (HC), and 51 healthy endemic donors (EC) by a quantitative enzyme-linked immunosorbent assay for reactivity with culture filtrate. Among the isotypes, significant differences between tuberculosis patient groups with either pulmonary or lymph node involvement and healthy control groups (HC and EC) were detected only for IgG (P < 0.001) and IgG1 (P < 0.001) antibodies. Pulmonary patients also showed a significant difference with IgM (P < 0.01) and IgE (P < 0.05) antibodies. HC showed elevation of only IgM antibodies compared with EC, indicating that IgM antibodies may be an indicator of recent infection with M. tuberculosis. These results suggest that the switching of IgM antibody response to IgG1 is a critical event in disease progression. Polyclonal IgG1, IgG3, and IgE antibodies also showed significant elevation (P < 0.05) in patients compared with EC. A strong correlation (rho = 0.254; P < 0.003) was observed between M. tuberculosis-specific IgG1 and polyclonal IgG1 in patients, suggesting that activations of antigen-specific and polyclonal antibodies are related events. No correlation was found between IgG1 antibodies and purified protein derivative skin test results. Since IgG1 antibody responses to culture filtrate are present only after disease establishment, IgG1 responses could provide a useful diagnostic marker of disease.