Cell was components from Streptococcus mutans NCTC 10449 and Streptococcus sanguis ATCC 10558 stimulated the release of 45Ca from prelabeled mouse calvariae in organ culture. Bone resorbing activity was not blocked by fetal calf serum. It was, however, blocked by calcitonin, an inhibitor of osteoclast-mediated bone resorption. Indomethacin, a prostaglandin synthetase inhibitor, partially blocked endogenous but not antigen-stimulated 45Ca, suggesting that antigen-stimulated bone resorption was not mediated by prostaglandins. The antigen preparations also had an inhibitory effect on the incorporation of 3H-proline and 3H-thymidine into explants of rabbit and rat calvariae, respectively. The inhibitory effect of antigen on 3H-proline incorporation was not altered by the presence of calcitonin, which suggests that it represented a real inhibition of protein synthesis and not a reflection that the bones were resorbing. These findings indicate that plaque bacterial antigens may contribute directly to the progressive loss of alveolar bone during periodontal disease. The assumption that only Gram-negative organisms play an important role In the etiology of periodontal disease appears incorrect.