Butyldiphenylchlorosilanes react with deoxy- and N-protected deoxymononucleotides to give, in each case, the 3'-O-butyldiphenylsilyl ether in high yield. A comparative study of n-, sec-, and tert-butyldiphenylchlorosilanes showed, as expected, a wide variation in the rate of formation and in the stability of the 3'-O-silyl ethers, the tert-butylphenylsilyl group being the one of choice in polynucleotide synthesis. The silyl group can be readily removed on treatment with fluoride ion in buffered pyridine at room temperature. This property markedly increases flexibility of the current methodology for polynucleotide synthesis. Secondly, because of its high lipophilicity, the silyl group allows rapid solvent extraction of synthetic intermediates, and thirdly, it greatly facilitates the isolation of the required product in synthetic reactions because of the selective and strong retention of the condensation product during reverse-phase high-pressure liquid chromatography. Several examples of synthetic procedures, including a stepwise synthesis of an undecanucleotide, are given which demonstrate overall simplification of polynucleotide synthesis.