It was investigated whether there was a relationship between p53 p21 and p27 induction pathways in the cellular response of glioma cells to hyperthermia. Two glioma cell lines were employed. A-172 cells had the wild-type of p53, and U251 cells had the mutant-type of p53. An adenovirus harbouring wild-type p53 was also used for the overexpression. The protein induction by hyperthermia was monitored by Western blot analysis. In U251 cells, the expression of wild-type p53 and hyperthermia had an additional cytotoxic effect, but did not affect A-172 cells. Significant p21 accumulation by hyperthermia was recognized in A-172 cells, and was also recognized in p53-transduced U251 cells. On the other hand, the accumulation of p27 by hyperthermia was not seen in A-172 or U251 cells, and the exogenous expression of p53 did not affect the accumulation of p27 by hyperthermia in U251 cells. These findings suggest that the p53-p21 pathway is involved in the signal transduction after hyperthermia, rather than the p27 pathway.