The effect of complete LNA substitution for a 2 0 -O-methyl RNA backbone was studied for the sequences 5 0 A L C L U L A L C L C L A L /3 0 r(UGAUGGU) and 5 0 G L C L U L A L C L U L G L / 3 0 r(CGAUGAC). As summarized in Table 2 , the stabilities of these duplexes at 37 C are within experimental error of those measured for 5 0 A M C L U M A L C M C L A M /3 0 r(UGAUGGU) and 5 0 G M C L U M A L C M U L G M /3 0 r(CGAUGAC), respectively. Evidently, the most effective use of LNA nucleotides is to space them every other nucleotide with the first LNA placed at the second nucleotide from the 5 0 end.