The production of scientific and technical knowledge is mostly concentrated in specific locations. Knowledge flows very easily within regions; however, scientific and technical knowledge does flow also between different regions. The aim of this article is to analyze knowledge flows between agglomerations of innovative inputs, and their effects on the innovative performance of regions. We estimate a regional knowledge production function and we test, through appropriate spatial econometric estimation techniques, the effect of both geographical and relational autocorrelation (as measured by participation to joint research networks in the European Union [EU] Sixth Framework Programme [FP6]). We adopt two selection criteria in order to define different relational "geographies" (hence spatial weights matrices), and we model the unobservable structure and link value of knowledge flows within these joint research networks. Our results confirm established evidence that knowledge flows within interregional research networks along a top-down nonsymmetrical and hierarchical structure. However, the EU enlargement - and a modified structure of incentive for collaboration activity of European institutions- changed the direction of knowledge flows toward a top-down dynamics of knowledge diffusion from coordinator to participants for "EASTWARD" research networks (whose coordinator is in the west and most participants in the east); while the contrary (a hierarchical bottom-up dynamic of knowledge transfer) is true for WESTWARD networks (whose coordinator is in the east and most participants in the west). FP6 is therefore a platform for knowledge barter exchange for EU15, while works as a mere one-way channel for knowledge diffusion from EU15 toward Central and Eastern European countries.