Porphyromonas gingivalis and Fusobacterium nucleatum are often coisolated from sites of infection, such as suppurative apical periodontitis. The synergistic pathogenicity of mixed infection of P. gingivalis HG 405 with F. nucleatum PK 1594 was studied in the mouse subcutaneous chamber model in groups of seven animals. The minimal dose for P. gingivalis HG 405 that was required to infect 100% of the chambers was reduced by 1,000-fold when animals were inoculated in the same chamber with 1 x 10(9)F. nucleatum PK 1594 (p < 0.001). To benefit from the presence of the fusobacteria, P. gingivalis HG 405 had to be coinoculated; inoculation in separate chambers for the same animal had no such effect (p < 0.001). Subinfective F. nucleatum inocula also benefited from the association with P. gingivalis HG 405 and uniformly established an infection when this partner was present (p < 0.001). These results suggest that the frequent and natural coexistence of P. gingivalis and F. nucleatum in diseased sites may express such a synergism in successful establishment and survival of small inocula.