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This paper introduces a Holistic Model of Acceptability and explores the potential of this model to identify the social context in which microbicides will likely be used once available. Data from qualitative in-depth interviews (n = 16) and quantitative surveys (n = 651) provide preliminary information. This effort represents a way to formally model likely microbicide use and is a starting point for future modeling work. A revised model for predicting microbicide use is suggested at the conclusion of the paper.