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The purpose of this study was to determine if relationships existed between institution type, single-sex versus co-educational, and science and mathematics scores of eighth-grade girls. We compared the mathematics and science performance of eighth-grade girls in three schools in a large school district in Texas: a single-sex (all-girls) school and two co-educational schools from the same district. A nonequivalent group, post-test only quasi-experimental design was utilized in the study to mitigate the effects of selection bias. We analyzed secondary data using multiple regression, controlling for race/ethnicity and socioeconomic status. The results suggest that students who attended the single-sex middle school scored significantly higher than students who attended the co-educational middle schools in both math and science.