In calculating tissue blood flow (TBF) according to the Fick principle, time-course information on arterial tracer concentration is indispensable and has a considerable influence on the accuracy of calculated TBF. In TBF measurement by xenon-enhanced computed tomography (Xe-CT), nonradioactive xenon gas is administered by inhalation as a tracer, and end-tidal xenon is used as a substitute for arterial xenon. There has been the assumption that the time-course change rate for end-tidal xenon concentration (Ke) and that for arterial xenon concentration (Ka) are substantially equal. Respiratory gas sampling is noninvasive to the patient and Ke can be easily measured by exponential curve fitting to end-tidal xenon concentrations. However, it is pointed out that there would be a large difference between Ke and Ka in many cases. The purpose of this work was to develop a method of determining the Ka value using the time course of tissue xenon concentration in Xe-CT. The authors incorporated Ka into the Kety autoradiographic equation as a parameter to be solved, and developed a method of least-squares to obtain the solution for Ka from the time-course changes in xenon concentration in the tissue. The authors applied this method of least-squares to the data from Xe-CT abdominal studies performed on 17 patients; the solution for Ka was found pixel by pixel in the spleen, and its Ka map was created for each patient. On the one hand, the authors obtained the average value of the Ka map of the spleen as the calculated Ka (Ka(calc)) for each patient. On the other hand, the authors measured Ka (Ka(meas)) using the time-course changes in CT enhancement in the abdominal aorta for each patient. There was a good correlation between Ka(calc), and Ka(meas) (r = 0.966, P < 0.0001), and these two Ka values were close to each other (Ka(calc) = 0.935 x Ka(meas) + 0.089). This demonstrates that K(cala) would be close to the true Ka value. Accuracy of TBF by Xe-CT can be improved with use of the average value of the Ka map of an organ like the spleen that has a single blood supply (only arterial inflow).