Lyme disease (LD) is caused by the tickborne spirochete Borrelia burgdorferi sensu lato and is the most common vectorborne disease in the United States. CDC initiated LD surveillance in 1982, and the Council of State and Territorial Epidemiologists designated it a nationally notifiable disease in 1991. This report summarizes the 17,730 cases of LD reported to CDC during 2000, which indicates that more LD cases were reported in 2000 than in any previous reporting year and that the reported incidence of LD is greatest in the northeastern, mid-Atlantic, and north-central regions of the United States. LD can be prevented by reducing tick populations, avoiding tick-infested habitats, using repellents, promptly removing attached ticks, and vaccination.