Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-(phosphonometoxy)prop-1-en-1-yl]adenine and a carbocyclic isosteric analog of guanosine monophosphate. The (Z)-and (E)-isomers inhibit the replication of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) and are nontoxic for cells. The (Z)-isomer activities against both viruses are higher than the (E)-isomer activities. Diphosphates of these compounds display substrate activities towards recombinant HSV DNA polymerase and HIV reverse transcriptase (RT). Diphosphate of the carbocyclic guanosine analog has no substrate activity towards HSV DNA polymerase but is active as a RT substrate.