OBJECTIVE. The purpose of our study was to test the hypothesis that the apparent diffusion coefficient (ADC) of normal-appearing white matter increases with advancing age. SUBJECTS AND METHODS, We selected 38 patients with normal MR imaging findings from 332 patients undergoing clinical MR imaging, Diffusion-weighted MR imaging was performed with diffusion gradients applied in three orthogonal directions, For each patient, the average ADC on trace-weighted diffusion images of white matter at prespecified regions of interest and at the thalamus were compared with the patient's age. RESULTS. For the white matter, ADC sorted by patient age in decades increased with advancing age. Patients at least 60 years old had significantly higher ADC (0.769 +/- 0.019 mm(2)/sec x 10(-3)) than patients less than 60 years old (0.740 +/- 0.013 mm(2)/sec x 10(-3)) (p < 0.001). Comparison of individual white matter ADC and age showed a significant increase with advancing age (p < 0.0001). For the thalamus, the average ADC among patients at least 60 years old (0.766 +/- 0.015 mm(2)/sec x 10(-3)) exceeded the average ADC for patients less than 60 years old (0.745 +/- 0.022 mm(2)/sec x 10(-3)) (p < 0.05). However, comparison of individual thalamic ADC and patient ages, although showing a trend to higher ADC with increasing age, did not reach statistical significance (p = 0.06). CONCLUSION. Advancing age is associated with a small but statistically significant increase of water diffusibility in human white matter. A similar trend was present in the thalamus, These increases may reflect mild structural changes associated with normal aging.