This article considers how different models of sexuality and disease converge and interact to co-produce understandings of HIV and AIDS, and the implications of inter-cultural communication for effective HIV prevention in diverse settings. In the Trobriands Islands of Papua New Guinea, the phenomenon of sovasova, or chronic illness that manifests when members of the same matrilineal clan have sexual relations, is a persuasive and problematic form of cultural knowledge that directly influences comprehensions of HIV and AIDS. As a social proscription, sovasova underscores cultural ideations about the importance of social exchange and the corporeal mixing of difference in sexual relationships. Trobrianders recognise clear signs and symptoms that herald the onset of sovasova, which are similar to descriptions of AIDS-related illness: weight loss, nausea, and malaise. Affected people use various herbal and magical treatments to effectively manage sovasova, and people can avoid the sickness altogether by simply not having sex with a fellow clan member. The cultural resources available for treatment allow people to regard transgression as a safe possibility, albeit socially undesirable. The broad comparisons that Trobrianders draw between sovasova and AIDS create tensions as people contemplate HIV prevention based on the cultural model of sexual disorder and the valued capacity and efficacy of sexuality in maintaining relations of difference.