Self and relational goals influence health behaviors. This investigation examined how these distinct motivations affect response to persuasive anti-smoking testimonials. While self vs. relational message cues failed to influence message response, findings indicated that dispositional levels of interdependence predicted more favorable message judgments when exposed to loss-framed, but not gain-framed messages. Furthermore, results showed that interdependence was a strong, positive predictor of character identification, an antecedent to both favorable message judgments and anti-smoking attitudes. Subsequent mediation analyses indicated that interdependence indirectly predicted favorable message judgments and anti-smoking attitudes through character identification. Although the relationship was substantially weaker, the findings also revealed an unexpected significant association between independent self-construal and character identification. Overall, the findings indicate that individual differences in self vs. relational goals contribute to the efficacy of persuasive appeals.