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We tested the effects of relational and instrumental message strategies on US residents' perception of rattlesnakes—animals that tend to generate feelings of fear, disgust, or hatred but are nevertheless key members of healthy ecosystems. We deployed an online survey to social media users (n = 1,182) to describe perceptions of rattlesnakes and assess the change after viewing a randomly selected relational or instrumental video message. An 8–item, pre–and post–Rattlesnake Perception Test (RPT) evaluated perception variables along emotional, knowledge, and behavioral gradients on a 5–point Likert scale; the eight responses were combined to produce an Aggregate Rattlesnake Perception (ARP) score for each participant. We found that people from Abrahamic religions (i.e., Christianity, Judaism, Islam) and those identifying as female were associated with low initial perceptions of rattlesnakes, whereas agnostics and individuals residing in the Midwest region and in rural residential areas had relatively favorable perceptions. Overall, both videos produced positive changes in rattlesnake perception, although the instrumental video message led to a greater increase in ARP than the relational message. The relational message was associated with significant increases in ARP only among females, agnostics, Baby Boomers (age 57–75), and Generation–Z (age 18–25 to exclude minors). The instrumental video message was associated with significant increases in ARP, and this result varied by religious group. ARP changed less in those reporting prior experience with a venomous snake bite (to them, a friend, or a pet) than in those with no such experience. Our data suggest that relational and instrumental message strategies can improve people's perceptions of unpopular and potentially dangerous wildlife, but their effectiveness may vary by gender, age, religious beliefs, and experience. These results can be used to hone and personalize communication strategies to improve perceptions of unpopular wildlife species. [ABSTRACT FROM AUTHOR]