BACKGROUND: The current reorganisation of the English NHS is one of the most comprehensive ever seen. This study reports early evidence from the development of clinical commissioning groups (CCGs), a key element in the new structures. AIM: To explore the development of CCGs in the context of what is known from previous studies of GP involvement in commissioning. DESIGN AND SETTING: Case study analysis from sites chosen to provide maximum variety across a number of dimensions, from September 2011 to June 2012. METHOD: A case study analysis was conducted using eight detailed qualitative case studies supplemented by descriptive information from web surveys at two points in time. Data collection involved observation of a variety of meetings, and interviews with key participants. RESULTS: Previous research shows that clinical involvement in commissioning is most effective when GPs feel able to act autonomously. Complicated internal structures, alongside developing external accountability relationships mean that CCGs' freedom to act may be subject to considerable constraint. Effective GP engagement is also important in determining outcomes of clinical commissioning, and there are a number of outstanding issues for CCGs, including: who feels 'ownership' of the CCG; how internal communication is conceptualised and realised; and the role and remit of locality groups. Previous incarnations of GP-led commissioning have tended to focus on local and primary care services. CCGs are keen to act to improve quality in their constituent practices, using approaches that many developed under practice-based commissioning. Constrained managerial support and the need to maintain GP engagement may have an impact. CONCLUSION: CCGs are new organisations, faced with significant new responsibilities. This study provides early evidence of issues that CCGs and those responsible for CCG development may wish to address.