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Methods of monitoring drug toxicity in off-target organs are very important in the development of effective and safe drugs. Standard 2-D techniques, such as histology, are prone to sampling errors and can miss important information. We demonstrate a novel application of optical computed tomography (CT) imaging to quantitatively assess, in 3-D, the response of adult murine spleen to off-target drug toxicity induced by treatment with the vascular disrupting agent ZD6126. Reconstructed images from optical CT scans sensitive to haemoglobin absorption reveal detailed, high-contrast 3-D maps of splenic structure and microvasculature. A significant difference in total splenic volume was found between vehicle and ZD6126-treated cohorts, with mean volumes of 61±3mm(3) and 44±3mm(3) respectively (both n=3, p=0.05). Textural statistics for each sample were calculated using grey-level co-occurrence matrices (GLCMs). Standard 2-D GLCM analysis was found to be slice-dependent while 3-D GLCM contrast and homogeneity analysis resulted in separation of the vehicle and ZD6126-treated cohorts over a range of length scales., (Copyright © 2015. Published by Elsevier Inc.)