Coxiella burnetii has two phase variants: highly virulent phase I and avirulent phase H. To examine the differences between the two phase variants in interaction with host response to infection, we performed experimental infection in immunodeficient mice. Experimental C. burnetii phase I infection in SCID mice suggested that innate immunity cannot control replication of the bacteria and that acquired immunity is essential for mice to survive infection. In this study, we used SCID and SCIDbg mice to determine whether phase II bacterial infection can be controlled in vivo.