The synthesis and anti-HCMV activity of novel 9-[[(ethoxyhydroxyphosphinyl)methoxy]methoxy]guanine 5, an isostere of PMEG monoethyl ester, are described. It has been demonstrated that phosphonate 5 showed comparable or greater anti-HCMV activity than ganciclovir against the AD-169 and Davis strains in tissue culture.