Much attention has been given to the photoradiation therapy, since its mechanism of effect is thought to be due to the cytotoxicity of singlet oxygen produced from hematoporphyrin derivative (HPD) by the light. We studied the effects of hyperthermia (HT) on cultured cells (T1) of ethylnitrosourea induced rat brain tumor which had uptaken HPD, because the extent of photopenetration is limited and the absorbed light is converted to heat. We used the T1 cells preincubated in Eagle MEM with 10% FCS and 2 micrograms/ml HPD, and estimated the cell survival by the colony formation using soft agar overlayer method. Synergistic effects of HT and HPD were recognized at the temperature over 41.5 degrees C-HT, suggesting that combined HT and HPD therapy could be a new promising technique. In these experiments, an increased cell proliferation was observed after temporary suppression by "insufficient hyperthermia" at 41.5 degrees C. This is a kind of rebound phenomenon, which has an important clinical implication. We should pay attention not only to the cell damage by HT but also to the outcome of the therapy which have received insufficient HT.