In Nova Scotia the main manifestation of acute Q fever is pneumonia, while in France it is granulomatous hepatitis. To test the hypothesis that the route of infection is the major determinant of the manifestations of acute Q fever, 10 groups of 10- to 12-g female BALB/c mice (4 animals/group) were used. Five groups were inoculated intraperitoneally (ip) and 5 intranasally (inl) with Coxiella burnetii. Both routes of infection resulted in pneumonia. However, the inl route resulted in greater airway changes (on a numeric scale with 0 being no changes): 2.05 +/- 2.20 versus 0.60 +/- 0.83 (P < .002). The ip route resulted only in hepatosplenomegaly. It was concluded that the route of infection is one determinant of the manifestations of acute Q fever.