OBJECTIVE: To investigate the ability of Actinomyces radicidentis to survive and establish in soft connective tissue that grew into subcutaneously implanted tissue cages in Sprague-Dawley rats. STUDY DESIGN: Known concentrations of A. radicidentis suspension, grown on blood agar and broth cultures, were inoculated into tissue cages in rats. The cage contents were retrieved after 7, 14, and 28 days for culturing and correlative light and transmission electron microscopy. RESULTS: Cell suspensions harvested from both types of cultures showed substantial decline in numbers in tissue cages during the observation period. However, correlative light and transmission electron microscopy revealed numerous aggregates of coccoid bacteria already by 7 days of observation compared with the formation of well established colonies with characteristic actinomycotic features by 14 days after inoculation. CONCLUSIONS: These results suggest that the pathogenicity of A. radicidentis is due to its ability to form large aggregates of cells held together by embedding themselves in an extracellular matrix in vital host tissues. Thus, A. radicidentis, like other pathogenic Actinomyces, existing in the protected biofilm-environment can collectively evade destruction and elimination by host defenses, including phagocytosis. tissue sections has been reached on the basis of demonstration of typical "ray-fungus" colonies (1,4) and by specific immunohistochemical staining of such colonies. (5,6) Since the advent of molecular methods, an unequivocal identification and typing of the organism has been achieved by molecular genetic methods, particularly by sequencing of 16s rRNA gene and by whole cell protein profiling. (7) Recently, two strains of previously not described actinomyces-like organisms were recovered in pure culture from root canals of two teeth with persistent apical periodontitis. (8) Evidence based on biochemical analysis, phenotypic characterization, whole-cell protein profiling and sequencing of 16s rRNA, the two isolates were found to be identical and has been proposed to be classified as a new species (7) , entitled Actinomyces radicidentis (Latin: radix dentis = out of the root of the tooth) and was validated. (9) The organism was isolated from two human teeth with persistent apical periodontitis. (8) No immunohistochemical or microscopic analysis of the periapical tissues of the two diseased teeth was done. As such, it was not possible to clarify whether the A. radicidentis established itself in extraradicular periapical tissue as periapical actinomycosis and prevented periapical healing in the two cases reported.(8) The question as to whether A. radidicidentis is an etiological agent of persistent apical periodontitis, therefore, remains unanswered. The key to the pathogenicity of Actinomyces israelii, the species most implicated in extraradicular periapical infections, seems to be its ability to form cohesive colonies consisting of branching filamentous organisms in host tissues. (4) A. radicidentis do not form bra...