The histopathologic features of experimental actinomycotic lesions produced in mice by Actinomyces israelii, Actinomyces naeslundii, and Actinomyces viscosus were examined. In lesions caused by A israelii the outer edge of the bacterial granule exhibited an eosinophilic fringe with no evidence of penetration of polymorphonuclear leukocytes (PMNs) into the bacterial granule. Chronic lesions after 6 weeks contained lobulated advancing fronts as well as areas of resolution showing heavy penetration by phagocytic cells. The number of macrophages and plasma cells in these lesions increased with time. In contrast, lesions caused by A viscosus and A naeslundii showed cellular evidence of resolution during the early stages of the infection (3-6 weeks). The bacterial core was readily penetrated and fragmented by PMNs in early A viscosus lesions. In lesions caused by A naeslundii there was less penetration of the central core by PMNs, and the bacterial granule tended to retain its structural integrity. Elongated crystals of hyaloid material appeared in lesions caused by all species. These protein-rich bodies appeared to be associated with resolving areas of the lesions. The observed contrast in the histopathologic appearance of actinomycotic lesions caused by A israelii, A naeslundii, and A viscosus is suggestive of important differences in the immune response of the host to infections caused by these three species.