The current study identified ethnic differences in beliefs about substance use and assessed their impact on frequency of use of various substances. Participants were 1,398 Caucasian and African-American rural secondary school students. Only tobacco or cigarettes had significant differences for both cognitive and frequency of use variables. Results revealed that Caucasian students reported higher past 12-month tobacco use compared to African-American students. Congruently, African-American students reported perceiving significantly greater wrongness in tobacco use. In contrast, Caucasian students had a significantly greater perception of harm of tobacco use compared to African-American students. When these cognitive variables were entered as mediators of the ethnicity-cigarette use relationship, only the attitude of wrongness variable served as a significant partial mediator. These data highlight the importance of addressing attitudes as part of substance use prevention.