Supramolecular polymers based on ureido-pyrimidinone (UPy) represent a promising class of biocompatible materials for medical applications. Here, the chemical modification effect of UV irradiation, used to sterilize these materials, is studied. Besides anticipated crosslinking effects, UV irradiation causes telechelic UPy-polymers to become fluorescent. UPy-model compounds confirm a relation between UV-induced changes and the UPy-moiety. UV-induced fluorescence and IR-spectral changes are (partially) reversible by heat and/or solvent treatment. The results indicate the presence of at least two distinct UV-induced molecular species. UPy-model compounds with specific tautomeric forms directly relate fluorescence to UPy-enol tautomers. Photo-enolization is hypothesized to occur via an excited-state intermolecular double proton transfer. Changes in UPy-tautomeric equilibrium and crosslinking are factors that influence the dynamics of UPy-based materials. Identification and understanding of such factors will aid in the successful application of these materials, for example as biomaterial in tissue engineering applications. (C) 2015 Wiley Periodicals, Inc.