Background: Health illiteracy is a societal issue that, if addressed successfully, may help to reduce health disparities. It has been associated with increased rates of hospital admission, health care expenditures, and poor health outcomes. Because of this, much of the research in the United States has focused on adults in the health care system. This study investigated the effect of aspects of health literacy on the motivation to practice health-enhancing behaviors among early adolescents. Methods: Measures were generally based on 3 National Health Education Standards for grades 5-8. Data were obtained from 1178 9- to 13-year-old students visiting 11 health education centers in 7 states. Students responded via individual electronic keypads. Results: Multivariate logistic regression revealed that, in addition to age, difficulty understanding health information and belief that kids can do little to affect their future health, decreased the likelihood for interest in and desire to follow what they were taught about health. Further, low interest independently decreased motivation to follow what was taught. Girls were more likely to turn to school, parents, and medical personnel for health information. Older students were more likely to turn to school and to the Internet. Conclusions: Programs and curricula should be designed to increase student interest in health issues and their self-efficacy in controlling their own health destinies. Educators should also teach students to more effectively use nonconventional health information sources such as the Internet, parents, and medical professionals.