As assessed by both standard histological staining and immunochemistry, intraperitoneal inoculation of C. burnetii in guinea pigs led to pathologic changes mainly in the liver, whereas intranasal inoculation led to pathologic changes mainly in the lungs. Myocarditis and positive blood cultures were observed only in those animals which received the highest inoculum. We therefore conclude that both the route of infection and the size of the inoculum influence clinical expression in acute Q fever.