Visualizing myelin in human brain may help the study of diseases such as multiple sclerosis. Previous studies based on T1 and T2 relaxation contrast have suggested the presence of a distinct water pool that may report directly on local myelin content. Recent work indicates that T2* contrast may offer particular advantages over T1 and T2 contrast, especially at high field. However, the complex mechanism underlying T2* relaxation may render interpretation difficult. To address this issue, T2* relaxation behavior in human brain was studied at 3 and 7 T. Multiple gradient echoes covering most of the decay curve were analyzed for deviations from mono-exponential behavior. The data confirm the previous finding of a distinct rapidly relaxing signal component (T2* ∼ 6 ms), tentatively attributed to myelin water. However, in extension to previous findings, this rapidly relaxing component displayed a substantial resonance frequency shift, reaching 36 Hz in the corpus callosum at 7 T. The component's fractional amplitude and frequency shift appeared to depend on both field strength and fiber orientation, consistent with a mechanism originating from magnetic susceptibility effects. The findings suggest that T2* contrast at high field may be uniquely sensitive to tissue myelin content and that proper interpretation will require modeling of susceptibility-induced resonance frequency shifts. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.