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Although meta-analyses of message framing effects on persuasion showed null differences between gain versus loss framing, this study suggests there are many reasons that message framing does produce different persuasive effects. Moderators (approach/avoidance motivation and prior behavior) and mediators (perception of framing and cognition/emotion) of framing on persuasion are tested by utilizing an experiment (N = 243) with a health-related message promoting flossing. Structural equation modeling analyses indicate that the moderators and mediators successfully completed the persuasion process from message framing to behavioral intention. Based on the results, we suggest six reasons that message framing effect produces different persuasion outcomes. [ABSTRACT FROM AUTHOR]