Three kappa-opioid receptor (KOR) mRNA isoforms have been detected in different parts of the central nervous system. At the cellular level, three KOR mRNA isoforms are also differentially distributed in the axons and cell bodies of adult mouse trigeminal neurons, as well as in the processes and cell bodies of differentiated P19 neurons. To determine the molecular basis underlying differential distribution of KOR mRNA isoforms, a GFP-fused RNA binding domain, MS2, was generated and used to trace movement of KOR mRNA tagged with the MS2-binding sequence in living neurons of dorsal root ganglia and in differentiated P19 neurons. The 5'- and 3'-untranslated regions (UTRs) of KOR, either alone or in combination, are able to mediate transport of mRNAs to processes of P19 neurons and axons of dorsal root ganglia. The efficiency of mRNA transport mediated by each 5'-UTR of KOR varies among the three isoforms; isoform A is most efficient. This study demonstrates the biological activity of the UTRs of KOR mRNA isoforms in directing differential transport of mRNA in mammalian neurons.