OBJECTIVE: The purpose of this study was to validate the utility of dual-source dual-energy MDCT in quantifying iodine concentration in a phantom and in renal masses. MATERIALS AND METHODS: A series of tubes containing solutions of varying iodine concentration were imaged with dual-source dual-energy MDCT. Iodine concentration was calculated and compared with known iodine concentration. Single-phase contrast-enhanced dual-source dual-energy MDCT data on 15 patients with renal lesions then were assessed independently by two readers. Dual-energy postprocessing was used to generate iodine-only images. Regions of interest were placed on the iodine image over the lesion and, as a reference, over the aorta, for recording of iodine concentration in the lesion and in the aorta. Another radiologist determined lesion enhancement by comparing truly unenhanced with contrast-enhanced images. Mixed-model analysis of variance based on ranks was used to compare lesion types (simple cyst, hemorrhagic cyst, enhancing mass) in terms of lesion iodine concentration and lesion-to-aorta iodine ratio. RESULTS: In the phantom study, there was excellent correlation between calculated and true iodine concentration (R(2) = 0.998, p < 0.0001). In the patient study, 13 nonenhancing (10 simple and three hyperdense cysts) and eight enhancing renal masses were evaluated in 15 patients. The lesion iodine concentration and lesion-to-aorta iodine ratio in enhancing masses were significantly higher than in hyperdense and simple cysts (p < 0.0001). CONCLUSION: Iodine quantification with dual-source dual-energy MDCT is accurate in a phantom and can be used to determine the presence and concentration of iodine in a renal lesion. Characterization of renal masses may be possible with a single dual-source dual-energy MDCT acquisition without unenhanced images or reliance on a change in attenuation measurements.