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To examine the effects of a theory-driven tobacco prevention program in sixth-grade children with a family tobacco cessation component implemented by school nurses in conjunction with the initiation of a statewide toll-free Quit Line.Self-report questionnaires completed by the sixth-grade children and their parents/guardians (N= 1024) representing largely rural southern school systems from disparate areas with high prevalence rates of tobacco use and lung cancer diagnoses. Pre- and posttest measures that evaluated the impact of both student and parent/guardian interventions were obtained over a 10-week period. Paired t-tests were used to examine differences between pre- and posttest scores for all student and parent/guardian variables. Repeated-measures analysis of variance was used to examine the effect of parent/guardian smoking on student pre- and posttest scores.The student program resulted in significant improvements in drug knowledge, refusal skills, attitudes, normative expectations, assertiveness, and anxiety reduction techniques. In addition, the effectiveness of several components of the tobacco prevention program for the children was impacted by the smoking status of their parents/guardians. Drug-use intentions and behaviors were lower at posttest for children from homes of nonsmokers versus children from homes of smokers. Parents/guardians consistently reported that smoking was detrimental to themselves, the public, and their children. Of those parents/guardians who identified themselves as smokers (26%) and received cessation materials, 46.4% indicated that the information motivated them to want to quit.Tobacco use continues to be the leading cause of preventable death in the United States, with greater than 2000 new youth becoming regular smokers each day. School nurses and nurse practitioners are in various pivotal positions to address tobacco and its related health concerns through delivery of effective family interventions that target children for tobacco prevention and parent/guardian smokers for cessation.