To test the effectiveness of a middle school, multimedia health sciences educational program called HEADS UP in non-Asian-minority (Hispanic and African American), inner-city students. The program designers hope to increase the number of these students entering the health sciences pipeline. The program includes video role-model stories featuring minority scientists and students, hands-on activities, and teacher resources. Collaborators from The University of Texas Health Science Center at Houston, Spring Branch Independent School District, and the Health Museum developed the modules. From 2004 to 2007, the authors used a quasi-experimental, two-group pretest/posttest design to assess program effects on students' performance and interest in science, their science self-efficacy, their fear of science, and their science-related careers self-efficacy. An independent third party matched the intervention school to a comparison school by test scores, school demographics, and student demographics and then matched pairs of sixth-grade students (N = 428) by fifth-grade science scores, gender, ethnicity, and participation in the free or reduced lunch program. The authors collected data on these students for three years. At eighth grade (2007), the intervention school students scored significantly higher (F = 12.38, P < .001) on the Stanford Achievement Test 10 in science and reported higher interest in science (F = 11.08, P < .001) than their matched, comparison-school pairs. Students in neither group reported an increase in their confidence to choose a science-related career, but students in one high-implementing teacher's class reported decreased fear of science. HEADS UP shows potential for improving inner-city, non-Asian-minority middle school students' performance and interest in science.