This study examines the content of and audience response to organ donation videos on YouTube, a Web 2.0 platform, with framing theory. Positive frames were identified in both video content and audience comments. Analysis revealed a reciprocity relationship between media frames and audience frames. Videos covered content categories such as kidney, liver, organ donation registration process, and youth. Videos were favorably rated. No significant differences were found between videos produced by organizations and individuals in the United States and those produced in other countries. The findings provide insight into how new communication technologies are shaping health communication in ways that differ from traditional media. The implications of Web 2.0, characterized by user-generated content and interactivity, for health communication and health campaign practice are discussed.