The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm 2 , a maximum some three times larger than that typically used for diffusion imaging. The signal decay with bfactor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 ร 15 ร 1 mm 3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 mm 2 /ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 mm 2 /ms. Simple models which might explain the non-exponential behavior, such as intra-and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm 2 , the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 mm 2 /ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.