Science education video game research points toward promising, but inconclusive results in both student learning outcomes and attitudes. However, student-level variables other than gender have been largely absent from this research. This study examined how students' reading ability level and disability status are related to their video game-playing behaviors outside of school and their perceptions about the use of science video games during school. Thirty-four teachers and 876 sixth- through ninth-grade students from 14 states participated in the study. All student groups reported that they would prefer to learn science from a video game rather than from traditional text, laboratory-based, or Internet environments. Chi-square analyses indicated a significant association between reading ability level, disability status, and key areas of interest including students' use of video games outside of school, their perceptions of their scientific abilities, and whether they would pursue a career in the sciences. Implications of these findings and areas for future research are identified.