The Study was undertaken to evaluate the alteration of thermal enhancement ratio as a function of time intervals between two split dose hyperthermias followed by irradiation. For the experiments, 330 mice were dibided into 3 group ; the first, 72 mice were used to evaluate the heat reaction by single dose hyperthermia and heat resistance by split dose hypertherima, the second, 36 mice were used to evaluate the radiation reaction by irradiation only, and the third, 222 mice were used for TER observation by combination of single dose hyperthermia and irradiation, and TER alteration by combination of split dose hyperthermia and irradiation. For each group the skin reaction score of mouse tail was used for observation and evaluation of the result of heat and irradiation. The results obtained are summarized as follow : 1. The heating time resulting 50% necrosis (ND50) was 101 minutes in 43$^{circ}C$ and 24 minutes in 45$^{circ}C$ hyperthermia, which indicated that there is reciprocal proportion between temperature and heating time. 2. Development of heat resistance was observed by split dose hyperthermia. 3. The degree of skin reaction by irradiation only was increased proportionally as a function of radiation dose, and calculated radiation dose corresponding to skin score 1.5(D1.5) was 4,137 rads. 4. Obtained thermal enhancement ratio by combination of single dese hyperthermia and irradiation was increased proportionally as a function of heating time. 5. Thermal enhancement ration was decreased by combination of split dose hyperthermia and irradiation, which was less intense and lasted longer than development of heat resistance. In summary, these studies indicate that the alteration of thermal enhancement ratio has influence on heat resistance by split dose hyperthermia and irradiation.