In the UK, as throughout Europe, policymakers are placing increasing emphasis on Regions, as units of social and economic agency. For example, universities are now seen as playing a key role in stimulating the Knowledge Economy on a regional basis. This paper will report on a case in the UK where institutions in one region are developing strategic and practical mechanisms for collaboration. The paper will highlight where positive opportunities are seen to exist; and identify some of the problems encountered in fulfilling the perceived potential of regional collaboration. The paper will identify issues which could form the basis of comparative (collaborative?) research, with the objective of identifying and disseminating successful practice drawn from regions in other parts of the world. The Higher Education Institutions (HEIs) in the East of England are engaged in an ambitious collaborative project, designed to increase the contribution the sector makes to economic and social innovation in the region (the i10 project, supported by the Higher Education Innovation Fund runs from April 2003 to March 2005. It involves all ten HEIs in the region: a diverse group of institutions with very different missions, traditions and practices. See www.i10.org.uk for further information). The project reflects an assumption made by UK policymakers that institutional collaboration, within a regional framework, will lead to benefits in terms of efficiency, effectiveness, and value for money. As such, the project has not been asked to question this assumption, but has frequently found itself confronting the issue in practical terms. This happened most recently, during discussions around whether - and if so on what scale - to seek funding to continue the project beyond its original 3 year life. Our research shows that regional institutional collaboration is problematic in a number ways. These include the prevailing climate and history of institutional autonomy; the numerous ways in which institutions - far from collaborating - are required to compete with each other; the diversity, or incoherence of institutional missions; the high cost of managing multi-party collaboration; dubious institutional commitment to the political aspirations associated with collaboration; and the questionable saliency of the region as an operational or cultural identity. The purpose of this paper is to review the experience of participants in the i10 project in the context of regional collaboration; and to draw out implications for policy and practice. It would be highly beneficial for us, and hopefully for other European partners, to have access to examples of successful collaboration, and to lessons learned in this context elsewhere in the world. By presenting a paper at this conference we would hope to identify comparable cases, which could together start to form a database of good practice for regional collaborators. While this proposal draws on experience gained in a project which promotes knowledge transfer and HE-business relationships, it would also be valuable to explore regional collaborative issues in the context of the 'core businesses' of teaching and research. And a forum which identifies good practice within regions is likely to create a promising platform for understanding how to improve practice which involves collaboration between regions.