Oligonucleotide hybridization to RNA has many applications, ranging from quantifying gene expression (18) (19) (20) 56) to designing therapeutics (4, 8, 21, 46, (52) (53) (54) . LNA nucleotides have characteristics useful for these purposes. For example, LNA usually stabilizes duplexes (4, 44, 48, 51) and is more resistant than RNA and DNA to nuclease digestion (4, 6, 51) . The results presented here provide insights that are useful for designing 2 0 -O-methyl RNA/LNA chimeric oligonucleotides for various purposes. Some trends may be general for RNA A-form helixes and thus may also be relevant to other chimeras with nucleotides that favor A-form conformations. The results suggest several principles for the design of 2 0 -O-methyl RNA/LNA chimeras for hybridization to RNA