Uniform heating of tumor tissue to therapeutic temperatures without damaging surrounding normal tissue is required for successful local heat therapy of cancer. We have previously shown that the mean temperature of solid tumors during microwave therapy can be selectively elevated above that of surrounding normal tissue with the adjunctive use of vasodilator drugs. We now propose a method of on-line treatment planning that will allow the therapist to minimize the standard deviation of measured intratumoral temperatures. The method requires hardware incorporating multiple (surface and/or interstitial) microwave applicators under control of a small computer together with software incorporating a novel control algorithm developed by the PI. With this system the entire measured temperature distribution may be continually reoptimized under closed loop control. The system infers relevant thermal parameters by analyzing responses of multiple temperature sensors as each of the power applicators is briefly turned off. Applied power is measured from transient slope changes of the temperature-time curves for each sensor. Then all power is briefly turned off, and effective perfusion is measured by thermal washout. By substituting these values into a system of linear equations derived from the bio-heat transfer equation, the small computer can calculate the optimal allocation of power among the various applicators ("knob settings") to generate most uniform intratumoral temperature distribution with the desired mean (or minimum) tumor temperature. We propose to develop a prototype system and to determine its utility in minimizing intratumoral temperature variations during microwave therapy. Thereafter, we propose a clinical study of the prototype system vs. a conventional multi-applicator system to test the hypothesis that a more uniform intratumoral temperature distribution will lead both to a lower incidence of complications caused by hot spots within the treatment field and to a lower incidence of treatment failures caused by cold spots within the tumor.