Following the recognition that 'culture matters' in designing effective public health programs, this paper focuses on one refraction of culture within the so-called 'homosexual' community in India, to highlight how attention to local knowledge and its socio-economic underpinnings can impact the politics of health care. Drawing primarily on ethnographic fieldwork conducted from 1995-1997 and 2003 in the South Indian city of Hyderabad among hijras (the so-called third sex of India) as well as the wider community of MSM or 'men who have sex with men', the paper argues that public health framings of homosexuality often fail to pay attention to differential understandings of stigma and their socio-economic underpinnings, a failure that accounts in some measure for the ineffectiveness of prevention programs targeted at 'high risk' communities such as hijras and MSM. Focusing on the local moral economy of respect and shame as one pathway of stigma and contagion, and in particular on the differences in constructions of respect and shame between hijras and the wider community of MSM, this paper points at one small way in which understanding how culture matters can ultimately address the ineffectiveness of prevention programs and redress the inequalities in health outcomes between the various margins and centers of power.