Purpose: To assess radio‐sensitivity of white matter fiber tracts interconnected to hippocampus. Methods: Twelve patients who had brain metastases and received fractionated whole brain radiation therapy (WBRT) (30 or 37.5G) were included in the study. Diffusion weighted images were acquired pre RT, end of RT, and 1 ‐month post‐RT. The fornix, cingulum and corpus callosum were extracted from diffusion weighted images by combining fiber tracking and segmentation methods based upon characteristics of the fiber bundles. The ingulum was segmented by a seed‐ based tractography, the fornix by an ROI‐based tractography, and the corpus callosum by a level‐set segmentation algorithm. The radiation‐induced longitudinal changes in diffusion indices of the structures were evaluated. Results: Significant percentage decreases were observed in fractional anisotropy in the cingulum posterior part, fornix, and corpus callosum from pre RT to end of RT by −14.0%, −12.5%, and −5.2%, respectively (p<0.001), and from pre RT to 1‐month post‐RT by −11.9%, −12.8%, and −6.4%, respectively (p<0.001). Moreover, significant percentage increases were observed in mean diffusivity in the corpus callosum and cingulum posterior part from pre RT to end of RT by 6.8% and 6.5%, respectively, and from pre RT to 1‐month post‐RT by 8.5% and 6.3%, respectively. Furthermore, significant percentage increases were observed in radial diffusivity anisotropy in the cingulum posterior part, fornix, and corpus callosum from pre RT to end of RT by 11.4%, 7.1%, and 17.0%, respectively, and from pre RT to 1‐month post‐RT by 10.5%, 4.9%, and 21.8%, respectively (p<0.001). The increase in radial diffusivity primarily contributed to the significant decrease in fractional anisotropy, indicating demyelination is the predominant radiation effect on the white matter structures. Conclusions: Our findings indicate the fornix and cingulum posterior part are susceptible to radiation damage, particularly to demyelination. Further investigation of the relationship between the structural damage and cognitive dysfunction is on‐going. Supported in part by National Institutes of Health grants RO1 NS064973.