BACKGROUND: South Africa, as an emerging middle-income country, is becoming increasingly influential in global health diplomacy (GHD). However, little empirical research has been conducted to inform arguments for the integration of domestic health into foreign policy by state and non-state actors. This study seeks to address this knowledge gap. It takes the form of an empirical case study which analyses how South Africa integrates domestic health into its foreign policy, using the lens of access to antiretroviral (ARV) medicines. OBJECTIVE: To explore state and non-state actors' perceptions regarding how domestic health policy is integrated into foreign policy. The ultimate goal of this study was to achieve better insights into the health and foreign policy processes at the national level. METHODS: Employing qualitative approaches, we examined changes in the South African and global AIDS policy environment. Purposive sampling was used to select key informants, a sample of state and non-state actors who participated in in-depth interviews. Secondary data were collected through a systematic literature review of documents retrieved from five electronic databases, including review of key policy documents. Qualitative data were analysed for content. This content was coded, and the codes were collated into tentative categories and sub-categories using Atlas.ti v.7 software. RESULTS: The findings of this work illustrate the interplay among social, political, economic and institutional conditions in determining the success of this integration process. Our study shows that a series of national and external developments, stakeholders, and advocacy efforts and collaboration created these integrative processes. South Africa's domestic HIV/AIDS constituencies, in partnership with the global advocacy movement, catalysed the mobilization of support for universal access to ARV treatment nationally and globally, and the promotion of access to healthcare as a human right. CONCLUSIONS: Transnational networks may influence government's decision making by providing information and moving issues up the agenda.