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Effective local hyperthermia for cancer requires selective elevation of intratumoral temperature without overheating of surrounding normal tissues. Temperature elevation depends upon the balance between absorbed power density, which heats the treated tissue, and blood perfusion, which cools it. Selectivity can be achieved by manipulations of vascular physiology to increase blood cooling of normal tissues or to decrease blood cooling of tumor tissue. Creation of a favorable normal-to-tumor blood flow ratio is possible because the small blood vessels supplying most tumors are structurally and functionally different from the microvasculature of normal tissues. Normal arterioles dilate in heated tissues to raise local blood flow; whereas tumor vessels generally do not. This difference in vascular responsiveness provides a target for selective drug action that can be exploited to enhance local heat therapy of tumors. Vasodilator drugs, in particular, have profound effects upon the distribution of blood flow between tumor and adjacent normal tissues. Dilation of normal arterioles improves blood flow in normal tissues and may also shunt blood away from the tumors. These effects have been demonstrated in small animals, in large animals, and in humans to varying degrees. Further clinical exploitation of the microvascular differences between tumors and adjacent normal tissues may lead to improved effectiveness of hyperthermia therapy for a variety of tumor types.