We previously reported that Macaca fascicularis immunized with formalin-killed Porphyromonas gingivalis were protected against the bone loss of periodontitis. To examine mechanisms of protection, we determined specific immunoglobulin G (IgG), IgM and IgA titers and opsonic capacities of sera from immunized and control animals. Serum IgG and IgA titers to P. gingivalis appeared early and persisted throughout the 36-week observation period. IgM titers were elevated until 6 to 12 weeks and then decreased through week 36. A significant association was observed between peak IgM titers prior to ligature placement and protection against bone loss (measured at week 30). In control monkeys, no significant IgG, IgA or IgM titers were seen. In sera from immunized animals, significant opsonic capacity was seen by 6-12 weeks and persisted throughout the study. In contrast, control sera showed only low opsonization capacity. Anti-P. gingivalis antibody titers in purified IgG, IgA and IgM fractions were determined by enzyme-linked immunosorbent assay, and opsonic activity was demonstrated only in the IgG fraction.