This study used qualitative content analysis to examine anonymous questions about sex and sexuality submitted by Latino and African American adolescents in Los Angeles, California, classrooms. The majority of questions asked about sexuality and sexual behavior, or anatomy and physiology, with fewer questions about pregnancy and pregnancy prevention, sexually transmitted infections, and condoms. Overall, a notable mix was found of questions implying exposure to or awareness of a wide range of sexual activities, together with questions demonstrating fundamental misunderstandings or confusion about some of the most basic aspects of sex and sexuality. Gender differences emerged across topics, subtopics, and question types. The results of this study suggest that differences exist between what Latino and African-American teens yearn to know about sex and sexuality, and what information they are getting on these topics from other sources. This reinforces the importance of considering the concerns and needs of the intended audience in designing and evaluating health education programs.