A cerebrospinal fluid (CSF)-suppressed flow-attenuated inversion recovery (FLAIR) double-shot diffusion echo-planar imaging (EPI) sequence was developed and used, along with a non-CSF-suppressed version of the sequence, to determine the extent of the contribution of CSF partial-volume averaging to the apparent diffusion coefficients (ADCs) of normal human brain in vivo. Regional analysis indicates that cortical gray matter and parenchymal tissues bordering the ventricles are most affected by CSF contamination, leading to elevated ADC values. Only slight differences in gray- and white-matter average ADCs were detected after CSF suppression. The human brain average ADCs calculated from high-resolution CSF-suppressed diffusion-weighted images in these studies are similar to those reported in animals. FLAIR diffusion sequences remove CSF as a source of error in ADC determination and ischemic lesion discrimination in diffusion-weighted images (DWI) and ADC maps.