Four pairs of sooty mangabey monkeys (Cercocebus atys) were inoculated with serial, 10-fold dilutions of Mycobacterium leprae. The highest-dose pair received 4.8 X 10(10) M. leprae. Serum samples were obtained and clinical signs of leprosy were recorded at intervals of 35 months. Longitudinal serum samples were assayed by an ELISA method for the presence of IgG and IgM antibodies to the M. Leprae-specific phenolic glycolipid-I (PGL-I) antigen. In general, the onset of disease symptoms paralleled the number of M. leprae inoculated, but the ultimate course of disease depended upon individual animal susceptibility. Both IgG and IgM anti-PGL-I isotypes were observed in variable levels and patterns, related to the disease stage, among the eight mangabeys. The data suggest that high IgG and low IgM anti-PGL-I levels correlated with less severe disease; whereas initial high IgM titers and/or rising or sustained high IgM titers, especially together with low IgG anti-PGL-I titers, preceded or corresponded to periods of progressive leprosy. The results show that IgG and IgM anti-PGL-I antibodies can be present in significant titers among mangabeys early after infection with M. leprae. It appears likely that the relative levels of these anti-PGL-I isotypes may be correlated with the susceptibility of individual animals to the development of lepromatous leprosy.