The authors attempted to determine whether a targeted educational intervention in an area with endemic Lyme disease could increase knowledge, positive attitudes, and reported behaviors related to tick bite prevention and consequently decrease tick bites, as measured by a biomarker of tick bites. Between April and September of 1999, 317 subjects in Baltimore County, Maryland, were randomized to receive either tick-related or general health-related educational materials bimonthly through the mail. At each of three clinic visits, participants completed a self-administered questionnaire and provided a serum sample. Anti-recombinant tick calreticulin antibody (ARTCA), measured in ng/ micro l, was used as a biomarker of tick bites. Linear and logistic regression analyses were used to determine 1) whether the educational intervention was associated with a change in knowledge, attitudes, and behaviors (KAB) and 2) whether change in KAB predicted change in ARTCA levels. Proportions of desired responses increased significantly among intervention subjects versus the comparison group on KAB measures related to examining the body for ticks and insect repellent use. Levels of ARTCA were low among all study subjects. Only six of 37 models exhibited a significant relation between change in a KAB variable and change in ARTCA levels over time. The behavioral intervention was associated with an increase in the KAB measures in the intervention group, but this change was not associated with change in ARTCA levels.