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Abstract Using the concepts of national and regional innovation systems as an analytical framework for analysing the cross-border networking activities between Baden and Alsace, the empirical analysis presented in this paper reveals that despite the political promotion of cross-border relations the reality in innovation networking looks different. In the industry sample used for empirical analysis, no firm in Baden had research contacts with an Alsatian research institute, while at least 7% of the Alsatian firms cooperated with research and transfer institutes in Baden. Although spatial distance does not matter, cultural and institutional distance does. The neighbouring region is not looked at as a significant knowledge source for firms in both regions. Despite technological and economic internationalization, for many firms innovation-relevant learning still takes place mainly within their own national and regional system of innovation. For the two regions under review, the Rhine is still a cultural and institutional barrier which needs more networking bridges to be crossed. [ABSTRACT FROM AUTHOR]