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S. L. Shapiro and colleagues (2006) have described a testable theory of the mechanisms of mindfulness and how it affects positive change. They describe a model in which mindfulness training leads to a fundamental change in relationship to experience (reperceiving), which leads to changes in self-regulation, values clarification, cognitive and behavioral flexibility, and exposure. These four variables, in turn, result in salutogenic outcomes. Analyses of responses from participants in a mindfulness-based stress-reduction program did not support the mediating effect of changes in reperceiving on the relationship of mindfulness with those four variables. However, when mindfulness and reperceiving scores were combined, partial support was found for the mediating effect of the four variables on measures of psychological distress. Issues arising in attempts to test the proposed theory are discussed, including the description of the model variables and the challenges to their assessment. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–14, 2009.