In order to be sustained within its enzootic cycle, B. burgdorferi must adapt to two strikingly different environments, the arthropod vector and the mammalian host. The ability to rapidly adapt to environmental changes is therefore presumed to be central to spirochete survival and pathogenic programs. Indeed, it has now been well established that tick feeding initiates extensive changes in both gene expression and protein composition, collectively referred to as "host adaptation," a process that is thought to continue throughout infection. The paucibacillary nature of borrelial infections, however, has hampered our ability to study this bacterium in vivo. To circumvent this limitation, an animal model was developed for obtaining sufficient numbers of organisms to directly examine differential gene expression and antigenic composition of B. burgdorferi within the context of the mammalian host. The DMC model allows for a direct comparison of host-adapted B. burgdorferi and their in vitro-cultivated counterparts.