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BACKGROUND AND PURPOSE: Recent improvements in MR gradient technology allow significant increases in diffusion weighting without prohibitive signal-to-noise degradation. The purpose of our investigation was to establish normative references for the signal intensity characteristics and apparent diffusion coefficient values of the adult brain at high b values. METHODS: Fifty adults underwent diffusion-weighted single-shot spin-echo echo-planar MR imaging. Isotropic diffusion-weighted images were obtained with b values of 0, 1,000, 2,000, 2,500, 3,000, and 3,500 s/mm2. Qualitative assessments were made in multiple regions of interest in gray and white matter. Three apparent diffusion coefficient maps were generated for each of six patients with a 2-point technique at a b value of 0 and at b values of 1,000, 2,000, and 3,000 s/mm2. RESULTS: Increasing b values result in a progressive decrease in the gray to white matter signal intensity ratio. Isointensity between gray and white matter results at b values between 1,000 and 2,000 s/mm2. At b values greater than 2,000, the gray-white pattern reverses relative to the usual b value of 1,000. Apparent diffusion coefficient values were shown to decrease with increasing b values. CONCLUSION: Attention to the reversal of gray-white contrast and the dependence of apparent diffusion coefficient on the b value are important in avoiding erroneous assignment of pathologic abnormalities to normal regions. This study provides the normative data for future diffusion investigations performed at high b values.