We developed a new protocol for the cyanoethylation of the hydroxyl function of nucleosides. A new system of Cs2CO3-tBuOH proved to be the best for the cyanoethylation. An oligonucleotide incorporating 2'-O-cyanoethylated uridine has high affinity (deltaTm = 0.6 degrees C/modification) for the complementary DNA or RNA strand than the corresponding 2'-O-methyl-RNA.