This article describes the distribution and management of drugs and supplies in scaling up access to public sector antiretroviral treatment (ART) in a middle-income country. More specifically, a case study of the Free State Province of South Africa is presented focusing on: the mobilisation and training of pharmaceutical staff for ART, processes related to the ordering, distribution and storage of medicines, continuity of ART supplies and the impact of ART delivery on other drugs and supplies. Data were obtained from longitudinal research conducted between April 2004 and July 2006 comprising three surveys of the first 20 health facilities providing ART in the province, key informant interviews and observations made of provincial ART Task Team meetings. The supply of ART in the Province was managed through the existing drug supply system but with special mechanisms to ensure integrity of ART supplies and security of stock within the existing supply system. Initial hiccups in the procurement of antiretroviral (ARV) drugs for South Africa (a national function) caused delays in putting patients on ART, although these supply problems were short-lived. At provincial level, not all pharmacist posts created for the programme were filled, and pharmacists working in the rest of the health system were subsequently trained to take on ART programme functions. Electronic systems were not established at all service sites, which in part contributed to delays in the delivery of drugs and supplies to more peripheral units. Adequate space to safely store ARV drugs remained problematic. The introduction of the ART programme did not create disruptions in the supply of non-ART essential drugs, which in fact improved over the period of observation. It is concluded that despite some process, human resource and infrastructural challenges, the drug management system in the Free State succeeded in incorporating public sector ART within its existing drug distribution network and functions, at least in the initial phase of scale up.