The usefulness of hypertermia for cancer therapy have well been established. The purpose of the present investigation was to ascess the effect of step-up $(42^{circ} o44^{circ}C;sequence)$ and step-down $(44^{circ} o42^{circ}C;sequence)$ heating on the skin of the hind foot of the mouse. Hyperthermic treatments were given by immersion the hind foot of the mouse in circulating water baths. Skin response was studied by the leg reaction, which was scored according to a numerical scoring system proposed by Urano et al (1980). The results were as follows 1. The skin damage of $44^{circ}C$ control group was more severe than $42^{circ}C$ control group (P<0.05), except for 15 min. heating group. 2. The Skin damage of step-down group was more severe than step-up group (P<0.05). 3. The skin damage of $44^{circ}C$ control group was more severe than step-up group when there is no difference in $44^{circ}C$ heating time of step-up group from 44"C control group (P<0.05). 4. In step-down group, the skin damage was more severe than $44^{circ}C$ control group after preheating 45 min at $44^{circ}C$ (P<0.05). Therefore, the above findings suggest the normal tissue damage by step-up heating was correlated with heating time of post step-up. The dropping of heating temperature in late phase had more severe damage of the skin than that in early phase during hyperthermia, and so contineous control of satisfactory temperature should be considered as the one of the most important factor for prognosis, complications of clinical hyperthermia