To determine the incidence and cumulative frequency of Lyme disease in a school-aged population in an area in which Lyme disease is endemic, serum specimens were obtained before and after the 1990-1992 tick seasons from 410 middle and high school students in southeastern Connecticut. Sera were tested for serologic evidence of infection with Borrelia burgdorferi, and students were questioned about physician-confirmed episodes of clinical Lyme disease. At enrollment, 29 (7%) students had a history of Lyme disease, and of these, 12 (41%) were seropositive for B. burgdorferi infection. Seronegative students (397) were followed prospectively over a total of 796 person years. At enrollment, 381 students (93%) had no history of Lyme disease, and of these, 1 (0.3%) was seropositive. During this period, 8 students developed clinical Lyme disease and 3 had asymptomatic infections with B. burgdorferi. The incidences of clinical Lyme disease and asymptomatic B. burgdorferi infection were 10.1 and 3.8 cases/1000 person-years, respectively. Lyme disease is an important health problem in school-aged children living in southeastern Connecticut.