Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted to humans by the bite of infected blacklegged ticks (Ixodes spp.). Early manifestations of infection include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. Left untreated, late manifestations involving the joints, heart, and nervous system can occur. A Healthy People 2010 objective (14-8) is to reduce the annual incidence of Lyme disease to 9.7 new cases per 100,000 population in 10 reference states where the disease is endemic (Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). This report summarizes surveillance data for 64,382 Lyme disease cases reported to CDC during 2003-2005, of which 59,770 cases (93%) were reported from the 10 reference states. The average annual rate in these 10 reference states for the 3-year period (29.2 cases per 100,000 population) was approximately three times the Healthy People 2010 target. Persons living in Lyme disease--endemic areas can take steps to reduce their risk for infection, including daily self-examination for ticks, selective use of acaricides and tick repellents, use of landscaping practices that reduce tick populations in yards and play areas, and avoidance of tick-infested areas.