OBJECTIVE: This study was performed to evaluate the radiosensitizing effect of combined administration of 13-cis-retinoic acid (cRA) and interferon-alpha-2a (INF) in normal cervical keratinocyte and cervical cancer cell lines. METHODS: cRA, INF and radiotherapy was applied to cervical cancer cell lines (HT-3 and HeLa cells) to obtain optimum dose 20% cytotoxicity in MTT assay from each treatment. The dose was determined as 1.8 Gy for radiation, 10uM for cRA, and 1,000 U/ml for INF. Primary cultured cervical keratinocyte (PCCK), HT-3 and HeLa cells were treated with cRA and INF alone or in combination and compared with untreated control cells. Finally, radiotherapy was added to the cRA and INF treatment. RESULTS: The treatment of cRA and INF-alpha reduced significantly the mean number of colony of HT-3 cells from 250 (SD, 19) to 143 (SD, 32). In contrast, PCCK and HeLa cells exhibited less than 15% reduction of colony formation with the treatment of cRA and INF-alpha. Irradiation of HT-3 cells reduced the colony formation significantly (from 63.6% to 18.4%, p=0.002) after treatment of cRA and INF-alpha. However, PCCK and HeLa cells showed 13.2% (from 70.0 to 56.8%, p=0.807) and 8.4% (from 60.8% to 52.4%, p=0.816) reduction of their colonies respectively. CONCLUSION: These results suggested that the treatment of cRA and INF-alpha showed significant radiosensitizing effect in HPV-negative HT-3 cells but not in the normal cervical cells or HPV-positive HeLa cervical cancer cells.