Syntheses of non ionic oligodeoxynucleoside phosphoramidates (P-NH 2) and mixed phosphorami-date-phosphodiester oligomers were accomplished on automated solid supported DNA synthesizer using both H-phosphonate and phosphoramidite chemistries, in combination with t-butylphenoxyacetyl for N-protection of nucleoside bases, an oxalyl anchored solid support and a final treatment with methanolic ammonia. Thermal stabilities of the hybrids formed between these new analogues and their DNA and RNA complementary strands were determined and compared with those of the corresponding unmodified oligo-nucleotides, as well as of the phosphorothioate and methylphosphonate derivatives. Dodecathymidines containing P-NH 2 links form less stable duplexes with DNA targets, d(C 2 A 12 C 2) (∆Tm/modification-1.4_C) and poly dA (∆Tm/modification-1.1_C) than the corresponding phosphodiester and methylphosphonate analogues, but the hybrids are slightly more stable than the one obtained with phosphorothioate derivative. The destabilization is more pronounced with poly rA as the target (∆Tm/modification-3_C) and could be compared with that found with the dodecathymidine methylphosphonate. The modification is less destabilizing in an heteropolymer-RNA duplex (∆Tm/ modification-2_C). As expected, the P-NH 2 modifications are highly resistant towards the action of various nucleases. It is also demonstrated that an all P-NH 2 oligothymidine does not elicit Escherichia coli RNase H hydrolysis of the poly rA target but that the modification may be exploited in chimeric oligo-nucleotides combining P-NH 2 sections with a central phosphodiester section.