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When conducting biological investigations, experts constantly integrate their conceptual and quantitative understanding of variation with the design and analysis of the investigation. This process is difficult for students, because curricula often treat these concepts as separate components. This study describes the effect of a curricular intervention aimed at improving students' conceptual and quantitative understanding of variation in the context of experimental design and analysis. A model-based intervention curriculum consisting of five short modules was implemented in an introductory biology laboratory course. All students received the regular laboratory curriculum, and half of the students also received the Intervention curriculum. Students' understanding of variation was assessed using a published 16-question multiple-choice instrument designed and validated by the research team. Students were assessed before and after the intervention was implemented, and normalized gain scores were calculated. Students who received the intervention showed significantly higher normalized gains than students who did not receive the intervention. This effect was not influenced by students' gender or exposure to prior statistics courses and persisted into and through the following semester's laboratory course. These results provide support for the use of model-based approaches to improve students' understanding of biological variation in experimental design and analysis.