The interaction of neuropeptides with post-synaptic receptors is characterised by a high entropic barrier originating from the combination of nanomolar concentration with low conformer population. The influence of high viscosity environments on conformer distribution can help overcome this difficulty. In an attempt to simulate the physicochemical conditions of the synaptic cleft, 15 N-labelled enkephalin has been studied in polyacrylamide gels swollen by different aqueous solutions in the temperature range 273^293 K. Nuclear Overhauser enhancement spectra in the gel pores are consistent with a conformational selection or a slowing down of internal motions that can favour the interaction of the peptide with the receptor. ß