Reduction of tumor blood flow during hyperthermia may impair the ability of the tumor vasculature to dissipate heat and lead to greater tumor cell killing. We are currently testing a new compound (KB-R8498) which has been found to reduce tumor blood flow. One hour after an i.v. or an i.p. injection of KB-R8498 the blood flow in SCK tumors of A/J mice was reduced to 40%–70% of control. The blood flow in 6 A/J mouse normal tissues one hour after drug treatment was mostly unchanged. Control tumors grew to four times the starting volume in 6 days. An injection of 10 mg/kg KB-R8498 caused a growth delay of about 2 days. After tumors were heated at 42.5°C for 60 min, there was a delay of 4 days in tumor growth. When i.p. or i.v. injections of KB-R8498 were given and the tumors were heated at 42.5°C for 60 min, there was a growth delay of over 10 days. The implications for clinical hyperthermia treatments are discussed.