In PET activation studies, linear changes in regional cerebral blood flow may be caused by subject interscan displacements rather than by changes in cognitive state. The aim of this study was to investigate the impact of these artifacts and to assess whether they can be removed by applying a scan-specific calculated attenuation correction (CAC) instead of the default measured attenuation correction (MAC). Two independent data sets were analyzed, one with large (data I) and one with small (data II) interscan displacements. After attenuation correction (CAC or MAC), data were analyzed using SPM99. Interscan displacement parameters (IDP), obtained during scan realignment, were included as additional regressors in the General Linear Model and their impact was assessed by variance statistics revealing the affected brain volume. For data I, this volume reduced dramatically from 579 to 12 cm(3) (approximately 50-fold) at P(uncorr) </= 0.001 and from 100 to 0 cm(3) at P(corr) </= 0.05 when CAC was applied instead of MAC. Surprisingly, for data II, applying CAC instead of MAC still resulted in a substantial (approximately 10-fold) reduction of the affected volume from 23 to 2 cm(3) at P(uncorr) </= 0.001. We conclude that interscan displacement-induced variance can be prevented by applying a (realigned attenuation correction scan (e.g., CAC). With MAC data, introducing IDP covariates is not an alternative since they model only this variance. Even in data with minor interscan displacements, applying a (realigned attenuation correction method (e.g., CAC) is superior to a nonaligned MAC with IDP covariates.