A series of new acycloguanosine O-alkoxyalkyl derivatives have been obtained by the reaction of 9-(2-hydroxyethoxymethyl)- and 8-bromo-9-(2-hydroxyethoxymethyl)-N2-acetylguanines with cyclic and acyclic alpha-vinyl ethers. 9-[2-(Alkoxyalkyl)oxyethoxymethyl]-N2-acetylguanines are better soluble in water and low-polar organic solvents as compared with acycloguanosine. The compounds have the pronounced antiviral activity against HSV-I in the experiments in vivo and can be applied as acycloguanosine prodrugs.