To assess single-breath-hold technique for ventilation mapping by using dual-energy computed tomography (CT) in phantom experiments and volunteers. Institutional review board approved this study, and written informed consent was obtained from all volunteers. A rubber bag filled with a mixture of xenon (0%-35.4%) and oxygen was scanned with dual-source dual-energy CT (80 kV and 140 kV with tin [Sn] filter [Sn/140 kV] and 100 kV and Sn/140 kV). A cylinder containing six tubes of identical sizes with different apertures was ventilated once with a mixture of 35% xenon and 65% oxygen and was scanned in dual-energy mode (80 kV and Sn/140 kV). Xenon-enhanced images were derived by using three-material decomposition technique. Four volunteers were scanned twice in dual-energy mode (80 kV and Sn/140 kV) during breath hold after a single vital-capacity inspiration of air (nonenhanced) and of 35% xenon. Xenon-enhanced images were obtained by using two methods: three-material decomposition and subtraction of nonenhanced from xenon-enhanced images. Regression analysis with t and F tests was applied to the data of the rubber bag scans, with the significance level set at .05. Mean pixel values of gas in the bag were linearly related to xenon concentration for all x-ray tube voltages (r(2) = 1.00, P < .00001). Pixel values of the xenon-enhanced images of the tubes were related to their aperture size. Nearly homogeneous (coefficient of variation: 0.22, 0.23, and 0.34) pixel values were found in the lungs of healthy volunteers, with higher pixel values in the trachea and lower pixel values in the bullae. Xenon-enhanced images calculated by using three-material decomposition had better image quality on visual comparison than those calculated by using subtraction. Xenon-enhanced dual-energy CT with the single-breath-hold technique could depict ventilation in phantoms and in four volunteers.