Lyme borreliosis (Lyme disease) is the most often reported arthropod transmitted disease in humans in the U.S.A. Although it has been reported from 43 states, cases are especially abundant in the mid-Atlantic and northeastern regions. Borrelia burgdorferi, the etiologic agent, is transmitted primarily by the western blacklegged tick (Ixodes pacificus) in far western North America, and by the blacklegged tick (Ixodes scapularis) in eastern North America. Although Lyme disease cases have been reported from southern states, some researchers doubt the presence of B. burgdorferi or of human Lyme disease in the south. However, new data show that B. burgdorferi is widely distributed in the south and that strains are genetically more varied than in the north. Moreover, B. burgdorferi enzootic cycles appear to be more complex and more tick species are identified as vectors of the spirochete in the southern states.