Telomeres are specialized structures at the ends of eukaryotic chromosomes which are composed of simple repetitive G-rich hexameric sequences. Activation of telomerase, a ribonucleoprotein that synthesizes telomeric DNA, is found in most malignant tumors. However, little data is available concerning the correlation between telomerase activity and NPC (nasopharyngeal carcinoma). In this study, telomerase activation was determined using the TRAP (telomerase repeat amplification protocol) assay in 62 nasopharyngeal biopsies (25 NPC, 25 non-malignant nasopharyngeal lymphoid tissues, 12 post-irradiated nasopharyngeal tissues). The results showed that strong telomerase activity was present in both NPC and non-malignant nasopharyngeal biopsies. Post-irradiated nasopharyngeal samples had a significantly lower telomerase activity than NPC and non-malignant nasopharyngeal lymphoid tissues. It is well known that nasopharyngeal tissue is infiltrated by numerous lymphocytes, which might retain telomerase activity. Therefore, the finding that the telomerase activation was lowest in post-irradiated nasopharyngeal tissues is reasonable because of the destruction of activated lymphocytes and NPC by radiation. NPC biopsies with positive lymph node involvement exhibited higher levels of telomerase compared to those without lymph node involvement. Our data indicate a positive association between telomerase activity and tumor potential for lymphatic spreading in limited local tumors. In addition, telomerase activity may be useful as a diagnostic marker in the detection of tumor cells in recurrent NPC, but not in primary NPC.