We found no reports that capsular-like polysaccharide antigen purified from Actinobacillus actinomycetemcomitans either induces osteoclastic bone resorption in mouse organ cultures or promotes osteoclast formation in mouse marrow cultures. In contrast, capsular-like polysaccharide antigen purified from A. actinomycetemcomitans strain Y4 induced bone resorption in mouse organ culture. To examine the mechanism of bone resorption induced by A. actinomycetemcomitans, mouse bone marrow cells were cultured with A. actinomycetemcomitans strain Y4 capsular-like polysaccharide antigen. A. actinomycetemcomitans strain Y4 capsular-like polysaccharide antigen stimulated osteoclast-like cell formation in mouse bone marrow cultures. However, the polysaccharide of A. actinomycetemcomitans lipopolysaccharide did not induce the formation of osteoclast-like cells. Indomethacin inhibited osteoclast-like cell formation mediated by A. actinomycetemcomitans strain Y4 capsular-like polysaccharide antigen in a dose-dependent manner. There was a good correlation between the number of osteoclast-like cells formed in the marrow culture and the amount of prostaglandin E2 released into the culture media. When mouse bone marrow cells were cultured with prostaglandin E2 during the culture periods, many osteoclast-like cells were formed. These results indicate that prostaglandin E2 is involved in the mechanism of the formation of osteoclast-like cells mediated by A. actinomycetemcomitans strain Y4 capsular-like polysaccharide antigen. A. actinomycetemcomitans strain Y4 capsular-like polysaccharide antigen may play an important role in inflammatory bone resorption by promoting osteoclast formation in periodontal disease.