BACKGROUND: The risk of acquiring Lyme disease has been evaluated by xenodiagnostic procedures with laboratory strains of Borrelia burgdorferi and laboratory-reared Ixodes ticks, or by clinical trials in which diagnosis was based on clinical findings, culture, or serologic tests. OBJECTIVE: Our purpose was to determine the risk of infection from tick bites in a natural setting in which wild strains of B. burgdorferi were involved, by a biopsy culture technique. METHODS: Skin biopsy specimens were obtained from Ixodes scapularis tick bite sites, processed, and examined for the presence of B. burgdorferi. RESULTS: B. burgdorferi was cultivated from only 2 of 48 skin biopsy specimens. In both instances duration of tick attachment was approximately 24 hours. CONCLUSION: In a hyperendemic region for Lyme disease the risk of infection after a deer tick bite appears to be low, particularly if the tick has been attached for less than 24 hours.