The correlation of the recognition properties of a molecularly imprinted polymer (MIP) with the recognition events in pre-polymerisation mixtures is of central importance to our understanding of the molecular imprinting technique. Using the NSAID naproxen as a model template, we have applied parallel theoretical (molecular dynamics) and practical ((1)H-NMR, X-ray crystallography, HPLC, radioligand binding) methods to examine the nature of template-functional monomer complexation. An effective imprint is achieved, despite the presence of only one site on the template which provides for the formation of effective electrostatic interactions with the functional monomer used, 4-vinylpyridine. This is attributed to the creation of a well-defined receptor site for the acidic terminus of the molecule and complementary van der Waals interactions, as described in preliminary simulations of the pre-polymerisation system, and as confirmed for the resultant MIP by HPLC data. Qualitative agreement is also observed between simulation and proton NMR data examining monomer self-association in the presence and absence of the template. On the basis of the data obtained, the role of a cross-linker appears to be more significant for this system than previously anticipated.