The explosive rise in Internet use calls for effective ways to utilize new forms of social media to enhance school smoking prevention programs. We attempted to design and test an educational intervention for youth tobacco prevention.Intervention design and posttest pilot implementation.A single high school in Athens, Greece.Two hundred twenty-five students (aged 15-18 years).A Facebook-integrated educational intervention in six simple steps was designed and tested during an ad hoc smoking prevention lecture to high school students in Greece in order to stimulate social mobilization in online networks.Number of students with an active Facebook account, percentage posting antismoking messages within a 72-hour period, number of Facebook friends reached.Descriptive statistics.Assessed 3 days after the lecture, 15.9% of students had posted a smoking-related sentence in their Facebook account, a take-home message that was spread as a note on their wall via news feed to their 20,095 cumulative Facebook friends.One smoking-related take-home message can spread virally to a large number of adolescents through their Facebook friends. This intervention provides insight into a novel way of providing health information to youth, a hard-to-reach and vulnerable population.