Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All compounds were tested for inhibition of several viruses, including human herpes simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds insignificantly inhibited human immunodeficiency virus type 1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'-deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in cell culture to corresponding thymidine.