Telomerase is an endogenous reverse transcriptase that uses its internal RNA moiety as a template for the synthesis of telomere repeats, thus maintaining telomere length. To study the susceptibility of telomerase to sugar-modified nucleotide analogs, inhibition by arabinofuranosylguanine 5'-triphosphate (araGTP), 3'-azido-2',3'-dideoxyguanosine 5'-triphosphate (AZdGTP), 2',3'-dideoxy-2'-fluoroarabino-furanosylguanine 5'-triphosphate (FaraGTP), and their thymine counterparts was investigated. Among these compounds, all dGTP analogs showed potent inhibitory activity against human telomerase. Conversely, dTTP analogs showed moderate or weak inhibition. Partially purified telomerase from cherry salmon testis utilized ddGTP and AZdGTP as substrates into the 3'-terminus of DNA.