During 2000, 49 states, the District of Columbia, and Puerto Rico reported 7,364 cases of rabies in nonhuman animals and 5 cases in human beings to the Centers for Disease Control and Prevention, an increase of 4.3% from 7,067 cases in nonhuman animals reported in 1999. Ninety-three percent (6,855 cases) were in wild animals, whereas 6.9% (509 cases) were in domestic species (compared wth 91.5% in wild animals and 8.5% in domestic species in 1999). Compared with cases reported in 1999, the number of cases reported in 2000 increased among bats, dogs, foxes, skunks, and sheep/goats and decreased among cats, cattle, horses/mules, raccoons, and swine. The relative contributions of the major groups of animals were as follows: raccoons (37.7%; 2,778 cases), skunks (30.2%; 2,223), bats (16.8%; 1,240), foxes (6.2%; 453), cats (3.4%; 249), dogs (1.6%; 114), and cattle (1.1%; 83). Ten of the 19 states where the raccoon-associated variant of the rabies virus has been enzootic reported increases in the numbers of cases of rabies during 2000. Among those states that have engaged in extensive wildlife rabies control programs, no cases of rabies associated with the epizootic of rabies in raccoons (or in any other terrestrial species) were reported in Ohio, compared with 6 cases reported in 1999. No rabies cases associated with the dog/coyote variant (compared with 10 cases in 1999, including 5 in dogs) were reported in Texas, and cases associated with the gray fox variant of the virus decreased (58 cases in 2000, including 38 among foxes). Reports of rabid skunks exceeded those of rabid raccoons in Massachusetts and Rhode Island, states with enzootic raccoon rabies, for the fourth consecutive year. Nationally, the number of rabies cases in skunks increased by 7.1% from that reported in 1999. The greatest numerical increase in rabid skunks (550 cases in 2000, compared with 192 in 1999) was reported in Texas. The number of cases of rabies reported in bats (1,240) during 2000 increased 25.4% over the number reported during 1999 (989) and represented the greatest contribution (16.8% of the total number of rabid animals) ever recorded for this group of mammals. Cases of rabies reported in cattle (83) and cats (249) decreased by 38.5% and 10.4%, respectively, whereas cases in dogs (114) increased by 2.7% over those reported in 1999. Reported cases of rabies among horses and mules declined 20% from 65 cases in 1999 to 52 cases in 2000. Four indigenously acquired cases of rabies reported in human beings were caused by variants of the rabies virus associated with bats. One case of human rabies acquired outside the United States that resulted from a dog bite was caused by the canine variant of the rabies virus.