We have reported that epinephrine injected intratumorally sensitized the effect of heat depending on the temperature of hyperthermia and dose of epinephrine. In this study the effect of the administration routes and timings of epinephrine was carried out using Lewis lung carcinoma growing in the hind legs of BDF1 mice. The effects were evaluated by tumor growth delay. The strongest sensitizing effect of epinephrine was obtained by the injection immediately before heating. The sensitizing effects were observed both on intratumoral injection and subcutaneous injection around the tumors. The strong effect was observed in high concentration (20%) and small amount (0.025 ml) of epinephrine injected intratumorously for small tumors (50 mm3). And in case for large tumors (250mm3) the stronger effect was observed in medium concentration (5%) and medium amount (0.1 ml) of epinephrine injected subcutaneously around the tumors. It seemed that these effects were depended on the infiltration of epinephrine to the blood vessels nearby the tumors. The site of injection and the amount of epinephrine should be taken into consideration.