Synergism was demonstrated between Sendai virus and Pasteurella pneumotropica in the respiratory tract of mice showing no evidence of previous infection with either agent. Mice aerosol challenged with P. pneumotropica invariably eliminated the viable organism from their lungs within 72 h. In contrast, intrapulmonary killing was delayed in animals previously infected with Sendai virus. Maximum synergism was observed when virus infection preceded bacterial challenge by 6 days. At this time, a mortality rate of 37% was observed as compared with 0, 10, 20, and 10%, respectively, in those animals in which the virus infection preceded bacterial challenge by 1, 3, 9, and 12 days. Previous immunization with Sendai virus completely prevented virus infection and thus the synergistic effect. Synergism with endogenous flora was also noted. Six days after virus infection an endogenous Pasteurella sp. began to proliferate in the bronchopulmonary tissues. Up to 10(4) colony-forming units per lung were recovered but no animals died of the endogenous Pasteurella infection.