We report herein the effects of p53 gene therapy in the radiotherapy or thermotherapy of eight human head and neck squamous cell carcinoma (SCC) cell lines. The discrepancy between radiosensitivity combined with p53 gene therapy than that without p53 gene therapy increased among the eight SCC cell lines. The discrepancy increased in the thermosensitivity at 43 degrees C and decreased in that at 44 degrees C among the eight SCC cell lines. Thus, the p53 gene therapy did not always improve the discrepancy between radiosensitivity and thermosensitivity in the eight SCC cell lines. In the radiotherapy combined with adenoviral p53 gene therapy, the survival rates of three of eight SCC cell lines decreased, and that of only one cell line increased compared with radiotherapy alone. In thermotherapy combined with p53 gene therapy, the survival rates of three at 44 degrees C and five at 43 degrees C of the eight SCC cell lines decreased, although only one cell line at 43 degrees C increased its survival rate compared with thermotherapy alone. The p53 gene therapy decreased the survival rates of both radiotherapy and thermotherapy in three of eight SCC cell lines. Further, the distribution of plots on the basis of the time for 10% survival of radiotherapy and the dose for 10% survival of thermotherapy with p53 gene therapy shifted to the lower left side of the plots compared with those without p53 gene therapy. These findings indicated that p53 gene therapy improves the effects of both radiotherapy and thermotherapy.