Expanded CUG repeats in the 3'-untranslated region (UTR) of the gene encoding myotonicdystrophy protein kinase (DMPK) cause myotonic dystrophy type 1 disease (DM1). Thepresence of such repeats has been found to impede gene expression at several levels in modelsystems. We took a bioinformatic approach to survey all human mRNA sequences forpolymorphic CUG repeats. Our survey revealed that CUG repeats occur widely in variousregions of mRNAs, with higher frequency in protein coding regions than 5’-UTRs or 3’-UTRs.About 30 genes were found to contain CUG repeats that are polymorphic in the number ofrepeats, suggesting the potential to expand or shrink. However, long polymorphic repeats wererestricted to the 3’-UTR of the DMPK gene and the coding region of the ribosomal protein L14gene. Using cell-free translation systems, we showed that extended CUG repeats can inhibitprotein synthesis in vitro in the rabbit reticulocyte lysate, but not in wheat germ extracts,consistent with our previous finding of an interaction of CUG repeats with the protein kinasePKR. In transfected cells, CUG repeats can inhibit gene expression both in cis and in trans.However, observations with PKR-minus cells indicate that these effects are not primarilyattributable to the interaction of extended CUG repeats with PKR. Northwestern blottingdetected the presence in human cells of more CUG-binding proteins than are currently known.