Mass media interventions are among the strategies recommended for youth cigarette smoking prevention, but little is known about optimal methods for reaching diverse youth audiences. Grades 4 through 12 samples of youth from four states (n = 1,230) rated smoking-prevention messages in classroom settings. Similar proportions of African American, Hispanic, and White youth participated. Impact of audience characteristics on message appeal ratings was assessed to provide guidance for audience segmentation strategies. Age had a strong effect on individual message appeal. The effect of gender also was significant. Message ratings were similar among the younger racial/ethnic groups, but differences were found for older African American youth. Lower academic achievement was associated with lower appeal scores for some messages. Age should be a primary consideration in developing and delivering smoking-prevention messages to youth audiences. The unique needs of boys and girls and older African American adolescents should also be considered. (Contains 2 figures and 2 tables.)