A precise understanding of human blood spin-spin relaxation is of major importance for numerous applications, particularly functional magnetic resonance imaging (fMRI), which is increasingly performed at 3 Tesla. It is well known that T-2 measured from partially deoxygenated blood depends on the Carr-Purcell Melboom-Gill (CPMG) refocusing interval (tau(180)) and on blood oxygenation (Y), yet debate remains over the quantification of this phenomenon, primarily with respect to the accuracy of its characterization by the diffusion and fast two-site exchange models. In this study, a detailed characterization of the deoxygenation-induced T-2 reduction in human whole blood, as well as a comprehensive assessment of the role of tau(180), were performed at 3 T. The diffusion model was found to better fit the observed T-2 behavior as compared with the exchange model. The estimated diffusion-model parameters suggest the T2 decay enhancement at 3 T is due to a linear increase in the magnitude of deoxygenation-induced field inhomogeneities with field strength. These findings also confirm the potential of tau(180) manipulation in measuring changes in venous blood volume. Magn Reson Mad 61:249-254, 2009. (c) 2009 Wiley-Liss, Inc.