Pulpal and periodontal diseases are bacterial infections which result in local connective tissue and bone destruction. Effective host resistance to these infections is primarily mediated by neutrophils and other phagocytic cells. PGG glucan (poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan) is a biological response modifier which stimulates the production of neutrophils and upregulates their phagocytic and bactericidal activity. In the present studies, the effect of PGG glucan on infection-stimulated alveolar bone resorption was tested in an in vivo model. Periapical bone resorption was induced in Sprague-Dawley rats by surgical pulp exposure and subsequent infection from the oral environment. Animals were administered PGG glucan (0.5 mg/kg) or saline (control) subcutaneously the day before and on days 2, 4, 6, 9, 11, 13, 16, and 18 following the pulp exposure procedure. PGG glucan enhanced the number of circulating neutrophils and monocytes and increased neutrophil phagocytic activity approximately two-fold. PGG glucan-treated animals had significantly less infection-stimulated periapical bone resorption than control animals, as determined radiographically (-48.0%; p < 0.001) and by histomorphometry (-40.8% and -42.4% for first and second molars, respectively; p < 0.001). PGG glucan-treated animals also had less soft tissue destruction, as indicated by decreased pulpal necrosis. Only 3.3% of the first molar pulps from PGG glucan-treated animals exhibited complete necrosis, as compared with 40.6% of pulps from controls. Finally, PGG glucan had no effect on either PTH- or IL-1-stimulated bone resorption in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)