Deoxyadenosine 5’- and 3’-dithiophosphate and thymidine 5’- and 3’-dithiophosphate were synthesized. These are the first examples of this class of compounds. Although several synthesis strategies were examined, the most successful involved coupling deoxynucleoside H-phosphonodithioates with 9-fluorenemethanol under oxidation conditions to generate deoxynucleoside 9-fluorenemethyl phosphorodithioates. Deprotection by treatment with concentrated ammonium hydroxide followed by HPLC purification yielded the deoxynucleoside dithiophosphates. These analogs showed modest inhibition of avian myeloblastosis virus reverse transcriptase. They failed to inhibit human immunodeficiency virus reverse transcriptase, alkaline phosphatase, T4 polynucleotide kinase, or DNA polymerase I Klenow fragment.