Human Lyme disease is a bacterial infection caused by members of the Borrelia burgdorferi s.l. complex that is transmitted primarily by ticks in the genus Ixodes. Since first reported in 1975 in Lyme, Connecticut, Lyme disease has steadily increased both in number of cases and geographic extent. Despite being restricted to eastern and midwestern states, Lyme disease is the 6th most common reportable disease in the US, with ~300,000 cases annually, of which only 10% are diagnosed because the spectrum of pathologies makes early diagnosis difficult. The forest-dwelling white-footed mouse, Peromyscus leucopus, is presently considered to be the main competent (amplifying) reservoir host, but our recent studies indicate the potential for a significant role in transmission of B. burgdorferi by the short-tailed shrews in the genus Blarina. Of 362 ticks removed from Blarina caught in live traps in eastern Virginia, 360 were Ixodes spp. Tissues from 22 of 33 Blarina from eastern Virginia were positive for B. burdorferi s.l., as were 72% of tissues from 25 museum specimens of Blarina collected from 1963-1993. Borrelia-positive tissues from Blarina collected in Minnesota (n = 42, 79%) and Kansas (n = 19, 74%) further indicate the importance of understanding the role of the short-tailed shrew in the transmission of Lyme disease.