Many anticancer treatments, including radiation therapy, have been demonstrated to work through apoptosis. The treatment of choice on nasopharyngeal carcinoma (NPC), a radiosensitive tumor, is radiotherapy. Apoptosis therefore provides a good model to predict or re-evaluate the therapeutic response in NPC. Cellular genes such as p53 and bcl-2 have been shown to be involved in apoptosis. Proliferating cell nuclear antigen (PCNA) is a useful marker for proliferating cells. This study was designed to investigate whether the expression of p53, bcl-2 and PCNA, evaluated on tumor specimens obtained at diagnosis, is indicative of the subsequent local recurrence and distant metastasis following radiation therapy. We analyzed the expression of p53, bcl-2 and PCNA by immunohistochemical methods from NPC specimens prior to radiation therapy. A total of 63 T3/T4 NPC patients including 10 patients with local relapse (Group I), 19 patients with distant metastasis (Group II), and 34 disease-free patients (Group III) were assessed. Six of the 10 (60%) group I NPC, 4 of the 19 (21.1%) group II NPC, and 13 of the 34 (38.2%) group III NPC exhibited positive p53 expression. For bcl-2 immunostaining, 8 of the 10 (80%) group I NPC, 10 of the 19 (52.6%) group II NPC, and 10 of the 34 (29.4%) group III NPC were positive. High PCNA labelling index was shown in 6 of the 10 (60%) group I NPC, 7 of the 19 (36.8%) group II NPC, and 5 of the 34 (14.7%) group III NPC. The bcl-2 and PCNA reactivity in NPC developing local recurrence after radiation therapy was significantly higher than that in the disease-free NPC (p < 0.05). These findings show that the overexpression of bcl-2 and high PCNA labelling index are probably related to local relapse in NPC patients receiving radiation therapy alone as primary treatment.