Since phenolic glycolipid-I (PGL-I) is an unequivocal marker of Mycobacterium leprae, the antigen has been a good candidate for the serodiagnosis and monitoring the effectiveness of leprosy chemotherapy. As an effort to define the kinetics of the PGL-I antigen and its antibodies in leprosy patients, this study was initiated to examine the serum specimens obtained serially from lepromatous patients under chemotherapy trials. PGL-I was detectable in 64 (94.1%) of 68 new lepromatous (bacterial index, BI = 3.2 to 5.8) and in 26 (78.8%) of 33 relapsed lepromatous patients (BI = 3.0 to 5.3). Meanwhile, virtually all of the new and relapsed patients were strongly seropositive to PGL-I. PGL-I was not detectable in any of the patients about 18 months after chemotherapy was initiated; however, anti-PGL-I reactivity declined by 50% at 2 years and by about 70% at 5 years after chemotherapy regardless of the drug regimens under study. Considering the rapid disappearance of the PGL-I antigen and steady decrease in anti-PGL-I IgM antibodies following chemotherapy, the PGL-I-based serology may be useful for monitoring the effectiveness of treatment, at both the early and late stages, in leprosy patients whose initial sera contain a significant level of PGL-I antigen or antibodies.