Administrative integration of disease control programmes (DCPs) within the district health system has been a health sector reform priority in South Africa for two decades. The reforms entail district managers assuming authority for the planning and monitoring of DCPs in districts, with DCP managers providing specialist support. There has been little progress in achieving this, and a dearth of research exploring why. Using a case study of HIV programme monitoring and evaluation (M&E), this article explores whether South Africa’s health system is configured to support administrative integration. The article draws on data from document reviews and interviews with 54 programme and district managers in two of nine provinces, exploring their respective roles in decision-making regarding HIV M&E system design and in using HIV data for monitoring uptake of HIV interventions in districts. Using Mintzberg’s configurations framework, we describe three organizational parameters: (a) extent of centralization (whether district managers play a role in decisions regarding the design of the HIV M&E system); (b) key part of the organization (extent to which sub-national programme managers vs district managers play the central role in HIV monitoring in districts); and (c) coordination mechanisms used (whether highly formalized and rules-based or more output-based to promote agency). We find that the health system can be characterized as Mintzberg’s machine bureaucracy. It is centralized and highly formalized with structures, management styles and practices that promote programme managers as lead role players in the monitoring of HIV interventions within districts. This undermines policy objectives of district managers assuming this leadership role. Our study enhances the understanding of organizational factors that may limit the success of administrative integration reforms and suggests interventions that may mitigate this.