LNA (Locked Nucleic Acids, 1, X = O, Y = O) is a novel oligonucleotide analogue capable of recognizing complementary DNA and RNA with unprecedented thermal affinities. Synthesis of the first chemically modified LNA analogues is reported. A 9-mer phosphorothioate-LNA containing three LNA thymine monomers (1, X = O, Y = S, Base = thymin-1-yl) and 9-mer LNAs containing one, three or five 2'-thio-LNA monomers (1, X = S, Y = O, Base = uracil-1-yl) were able to recognize both complementary DNA and RNA with thermal affinities comparable to those of parent LNA.