The aim of the present study was to determine the role of antibodies specific to anti-surface-associated material from Actinobacillus actinomycetemcomitans (anti-SAM-Aa) in an infection induced by this periodontopathogen in mice. When SAM-Aa obtained by saline extraction of A. actinomycetemcomitans Y4 was separated on one-dimensional gel electrophoresis, this constituent contained antigen fragments with molecular weights ranging from 14 000 to 79 000. Immunoblot analysis revealed that increased antigen dose/immunization resulted in increased numbers of antigen epitopes recognized by serum antibodies of the immunized mice. Rapid healing of the primary lesions and high levels of specific IgG antibodies after challenge with live A. actinomycetemcomitans were seen in the immunized mice, especially at the highest-dose level of 100 μg/immunization. Transfer of SAM-Aa-immunized, but not the SAM-Aa–immunized and adsorbed, serum prior to challenge with live bacteria led to rapid healing of the lesions in the recipient mice. Increased phagocytosis of A. actinomycetemcomitans by murine macrophages (RAW264.7 cells) was observed when this periodontopathogen was opsonized by the SAM-Aa-immunized, but not SAM-Aa-immunized and adsorbed, serum. These results suggest that in mice, SAM-Aa antigens may induce protective antibodies by acting, at least, as an opsonin against challenge with live A. actinomycetemcomitans.