Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and of 28 tuberculoid leprosy patients reacted in a significant manner to 29/33-kilodalton (kDa) doublet and 64-kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed a significantly high immunoglobulin G antibody titer to the purified M. tuberculosis 29/33-kDa doublet and 64-kDa antigens in lepromatous and tuberculoid leprosy patients, respectively, as compared with normal subjects and tuberculosis patients. This enzyme-linked immunosorbent assay serology may be useful for distinguishing two polar types of leprosy and for diagnosing leprosy in general.