A variety of methods have been developed to prevent human infection by the Lyme disease spirochete in the northeastern United States, mainly based on the observations that nymphal Ixodes dammini serve as vector, that deer serve as hosts for the reproductive stage of this tick, that white-footed mice serve as the reservoir of infection, and that nymphs are most abundant in early summer and must attach for 2 days before infection is transmitted. Methods for personal protection included seasonal avoidance of infested sites, the use of repellants, and prompt removal of attached ticks. Destruction of mouse habitat, but not of mice, was locally effective. Nondestructive acaricidal treatment of deer proved ineffective, but the elimination of these hosts resulted in reduced transmission after several years. Treatment of mice by means of acaricide-impregnated bedding material effectively reduced transmission.