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Background: Lyme disease (LD) is the most common tick-borne disease in the United States and in Europe. The aim of this study was to examine knowledge, perceived risk, feelings of anxiety, and behavioral responses of the general public in relation to tick bites and LD in the Netherlands. Methods: From a representative Internet panel a random sample was drawn of 550 panel members aged 18 years and older (8-15 November 2010) who were invited to complete an online questionnaire. Results: Response rate (362/550, 66%). This study demonstrates that knowledge, level of concern, and perceived efficacy are the main determinants of preventive behavior. 35% (n = 125/362) of the respondents reported a good general knowledge of LD. While 95% (n = 344/362) perceived LD as severe or very severe, the minority (n = 130/362, 36%) perceived their risk of LD to be low. Respondents were more likely to check their skin after being outdoors and remove ticks if necessary, than to wear protective clothing and/or use insect repellent skin products. The percentage of respondents taking preventive measures ranged from 6% for using insect repellent skin products, to 37% for wearing protective clothing. History of tick bites, higher levels of knowledge and moderate/high levels of worry were significant predictors of checking the skin. Significant predictors of wearing protective clothing were being unemployed/retired, higher knowledge levels, higher levels of worry about LD and higher levels of perceived efficacy of wearing protective clothing. Conclusions: Prevention programs targeting tick bites and LD should aim at influencing people's perceptions and increasing their knowledge and perceived efficacy of protective behavior. This can be done by strengthening motivators (e.g. knowledge, concern about LD, perceived efficacy of wearing protective clothing) and removing barriers (e.g. low perceived personal risk, not knowing how to recognize a tick). The challenge is to take our study findings and translate them into appropriate prevention strategies. [ABSTRACT FROM AUTHOR]