Functional MR (fMR) has been useful in providing insight into the localization and detection of neural cortical activity. However, patient head motion is inevitable over the course of most fMR experiments. Although methods to align the control and activation fMR images may correct for some of this motional error, they will be incomplete in correcting for those that depend on spatial orientation. MR signal amplitude of structures that lie along air-tissue interfaces, for example, are sensitive to susceptibility errors introduced by their reorientation with respect to the main magnetic field. This analysis, using phantoms, cadaver brain, and volunteers, has shown that this reorientation between control and activation images can create regions of "false activation" that increase in area with rotation. Anatomic regions that are expected to be most affected by these susceptibility-induced magnetic field homogeneity variations are those adjacent to bone or air, such as the mesial and inferior temporal lobes and the inferior and anterior frontal lobes. Interpretation of "activation" in these areas on fMR studies must be performed with careful consideration of this important source of error.