PURPOSE: To determine the imaging characteristics of a new computed tomographic (CT) contrast material with both hepatocyte-selective and blood-pool components (iodinated triglyceride (ITG)-dual) versus standard iohexol. MATERIALS AND METHODS: VX2 carcinoma was inoculated in seven rabbits. Animals underwent nonenhanced, iohexol-enhanced (600 mg of iodine per kilogram of body weight), and ITG-dual-enhanced (blood-pool moiety, 100 mg of iodine per kilogram; hepatocyte-selective moiety, 100 or 200 mg of iodine per kilogram, injected 90 minutes apart) helical CT. Livers were removed, preserved in formalin, suspended in agar, and sectioned transversely at 3-mm intervals. Attenuation values for normal liver and tumors were obtained, and blinded readers evaluated images for lesions by using a modified free-response receiver operating characteristic (ROC) method. RESULTS: A total of 47 separate tumor sites were detected at pathologic examination. ITG-dual-enhanced scans obtained with 300 mg of iodine per kilogram demonstrated similar liver opacification to iohexol-enhanced scans obtained with 600 mg of iodine per kilogram, but with less lesion enhancement, which resulted in better liver-to-lesion contrast. Blinded readers had a higher sensitivity, accuracy, and area under the ROC curve for ITG-dual-enhanced scans as compared with iohexol-enhanced scans (P < .01). CONCLUSION: ITG-dual-enhanced CT quantitatively and qualitatively improved liver lesion detection versus iohexol-enhanced CT. Future clinical trials with various human tumor types after potential approval for human use are needed to determine the ultimate role of this or other dual-mechanism contrast materials.