To better understand the motivation for adolescent smoking and drinking and to identify the underlying risk and protective factors associated with these behaviors among adolescents. Cross-sectional, school-based survey of students in grades 5 through 12. A nationally representative sample of 2574 boys and 2939 girls in grades 7 through 12 from 297 public, private, and parochial schools across the United States who participated in The Commonwealth Fund Survey of the Health of Adolescent Girls and Boys in 1997. Sex-specific adjusted relative risks (RRs) and 95% confidence intervals (CIs) comparing self-reported regular smokers and regular drinkers by risk and protective factors with adolescents reporting none of these behaviors. Adolescent boys and girls were equally likely to be regular smokers (11.2%). The prevalence rate of regular drinking was only slightly higher for boys (22.4%) than it was for girls (19.3%). The rates of both health-risk behaviors were significantly higher for those reporting risk factors, and the strengths of associations varied by sex. Sex differences also emerged in motivation for engaging in these behaviors. When we adjusted for demographic characteristics, exposure to childhood abuse (RR, 4.1; 95% CI, 2.4-7.0) and stressful life events (RR, 2.4; 95% CI, 1.1-5.4) were strongly associated with increased risk for boys' regular smoking. Similar associations were found for regular drinking. For girls, a history of abuse (RR, 1.8; 95% CI, 1.1-2.8), violence within the family (RR, 2.2; 95% CI, 1.6-3.2), depressive symptoms (RR, 1.6; 95% CI, 1.0-2.4), and stressful life events (RR, 3.1; 95% CI, 1.8-5.6) were significantly associated with increased risk for regular smoking. Similar associations were again found for regular drinking. Parental support was protective against both health-risk behaviors for both sexes. Participation in extracurricular activities was associated with lower risk for regular smoking for boys (RR, 0.4; 95% CI, 0.2-0.7) and for girls (RR, 0.3; 95% CI, 0.2-0.5); however, there was no significant association between drinking behavior and participation in activities. The increased risk for regular smoking and regular drinking among adolescents with a history of abuse, family violence, depressive symptoms, and stressful life events suggests that routine screening for abuse, violence, and other family experiences should be an essential component of adolescent health care visits. Effective prevention programs to reduce smoking and drinking among adolescents should recognize that health-risk behaviors may be associated with other negative life experiences and that the strength of these associations differs by sex.