From 1979 to 1983, Lyme disease was studied longitudinally in the 162 long-term residents of Great Island, Massachusetts. In retrospect, the index case occurred in 1962, and the peak years of disease transmission (about three new cases per 100 residents per year) were the late 1970s. Thereafter, during the period of active surveillance, attack rates declined by half. Altogether, 26 (16%) of the 162 residents developed symptoms of the disease. Most of those affected had erythema chronicum migrans, and when untreated, they subsequently developed arthritis or, in one instance, myocarditis. A minority of individuals, mostly children, had arthritis alone. Of 121 asymptomatic residents who gave blood samples, 10 adults (8%) had high titers of IgG antibodies to the Lyme disease spirochete; these titers sometimes persisted for years. From 1981 to 1983, the estimated ratio of apparent-to-inapparent infection was 1:1. The high frequency of Lyme disease on Great Island underscores the need for surveillance and control programs.