In this study, we review annual rabies data from Massachusetts from 1985 to 2006, spanning the introduction of raccoon strain rabies in 1992. Of 52,034 animals tested, 9.7% (5,049/52,034) were rabid, representing 26 of over 67 species submitted. Bats were the most common rabid animals prior to 1992 (50 of 52), but raccoons (Procyon lotor) became the most common rabies-positive species upon arrival of raccoon strain rabies virus (38.2%, 2,728 of 7,138 tested), followed by striped skunks (Mephitis mephitis, 34.4%, 1,489 of 4,332), bats (5.3%, 427 of 8,053), foxes (red fox, Vulpes vulpes, and gray fox, Urocyon cinereoargenteus, 16.3%, 135 of 827), cats (0.8%, 136 of 18,050), and woodchucks (Marmota monax, 5.7%, 82 of 1,446). Cats were the most frequently tested animal (34.7%). Raccoon strain rabies spread from two foci of introduction with an initial epizootic phase of 4 yr, by which time most of the state was affected. In 1992, there was a transition from enzootic bat rabies, with little spillover to other animals, to terrestrial rabies associated with raccoon strain virus. Although raccoons were most affected by the raccoon strain virus, there was spillover to other species, particularly to skunks. The eastern United States raccoon rabies epizootic led to a marked increase in submissions for rabies testing and the number of positive animals detected; however, bat rabies cases remained at their previous levels. Wild animal rabies presents a significant threat to humans and domestic/companion animals and increased costs related to increased demand for rabies testing, postexposure prophylaxis as well as euthanasia of valuable domestic animals.