This article provides an extended, comprehensive example of how teachers, schools, districts, and external factors (e.g., parental pressure and policy mandates) shape curriculum research in the U.S. It retrospectively examines how three different middle school curriculum units were implemented and scaled-up in a large, diverse school system. The curriculum materials were cognitively based, hands-on, guided inquiry units; each focused on a different "big idea" in science. The units met some criteria for instructional strategies rated by the Project 2061 Curriculum Analysis. Using evidence-based decisions, two of the units were found to be effective and equitable, and went to scale, but one was not effective. However, the course of scale-up was also affected by a changing policy climate, and proceeded in unpredictable ways, with small scale effects not found at large scale, and experienced teachers less effective than inexperienced teachers. Four years after funding ended, none of the units were sustained within the school district. The interactions between the demands of the units and of the school district's policy environment suggests reasons why this occurred, despite evidence that two of the units were successful with diverse learners. (Contains 5 figures and 1 table.)