BACKGROUND: Serological tests can be important tools to assist in the diagnosis of leprosy and can contribute to an earlier diagnosis. The aim of this study was to evaluate the antibody responses against phenolic glycolipid-1 (PGL-1), natural disaccharide linked to human serum albumin via an octyl (NDO-HSA), Leprosy IDRI Diagnostic-1 (LID-1) and natural disaccharide octyl--Leprosy IDRI Diagnostic-1 (NDO-LID) in leprosy patients, household contacts of patients and the general population. METHODS: Enzyme-linked immunosorbent assays were used to analyze the antigen-specific antibody responses of 94 leprosy cases, 104 household contacts of cases and 2.494 individuals from the general population. RESULTS: A positive correlation was observed for the antibody responses to all antigens studied. A higher proportion of seropositivity for all antigens, along with stronger magnitude of response, was observed in multibacillary (MB) leprosy patients and household contacts of MB leprosy patients compared with the levels observed in paucibacillary (PB) leprosy patients and household contacts of PB leprosy patients. A substantial and significant positive correlation was found between seropositivity and the bacterial index for the leprosy patients. Anti-PGL-1 tests were more frequently positive than anti-NDO-HSA tests among patients with all clinical forms of leprosy and among the group of household contacts. The LID-1 and NDO-LID antigens showed a greater capacity to identify household contacts and individuals from the general population infected with M. leprae. CONCLUSIONS: Tests that measure the antibody responses against LID-1, NDO-LID, NDO-HSA and PGL-1 were effective tools for the detection of patients with MB leprosy. Our data indicate that the anti-LID-1 and anti-NDO-LID responses were more effective than an anti-NDO-HSA response for the identification of individuals with subclinical infection.