The Mycobacterium leprae-specific antibody assays--a serum antibody competition test (SACT-ELISA) for the epitope on the 35-kDa protein, and an enzyme immunoassay for the disaccharide epitope of phenolic glycolipid-I (PGDS-ELISA)--were evaluated as tools for the serological monitoring of chemotherapy in 20 lepromatous and 6 tuberculoid leprosy patients. In addition to estimates for M. leprae-specific antibodies, assessments of the bacterial index (BI) and clinical activity of the disease were also carried out prospectively in these patients on two to four occasions over a period of 19 months. In most cases, a decline in the BI, clinical scores, and antibody levels was observed during the course of treatment. The relative rate of decline was steepest and least variable with the SACT-ELISA, followed by the PGDS-ELISA and the BI. In some patients who showed a static or even an increased BI, despite marked clinical improvement, the antibody levels decreased. These data indicate that, unlike the BI, there is a greater dependence of specific antibody levels on the viability of M. leprae. This, combined with the fact that antibody titers would reflect the antigen load in the whole body, makes M. leprae-specific serology a promising tool for monitoring chemotherapy in leprosy patients.