Oligodeoxyribonucleotides with phosphonoacetate or thiophosphonoacetate internucleotide linkages can be made in high yield by solid-phase synthesis and possess many advantages. They are highly stable to nucleases, water-soluble, and anionic at neutral pH. They form stable duplexes with DNA and RNA, and stimulate RNase H degradation of complementary RNA. The preparation of the N,N-(diisopropylamino)phosphinyl acetate monomers from standard protected nucleosides is described here, followed by the synthesis of phosphonoacetate and thiophosphonoate oligodeoxyribonucleotides, as well as chimeric oligomers that have these modified linkages in combination with natural or phosphorothioate linkages. Purification and characterization of these oligomers is also presented.