It is recognized that scatter correction can supply more accurate absolute quantification, and that iterative reconstruction results in better noise properties and significantly reduces streak artefacts; however, it is not entirely clear whether they produce significant changes in [18F]-FDG distribution of reconstructed 3D brain PET images relative to not scatter corrected images and analytic reconstruction procedures. The current study assesses the effect of model-based scatter correction using the single-scatter simulation algorithm and iterative reconstruction in 3D brain PET studies, using statistical parametric mapping (SPM) analysis. The study population consisted of 14 healthy volunteers (6 males, 8 females; age 63-80 years). PET images were reconstructed using an analytic 3DRP reprojection algorithm with (SC) and without explicit scatter correction (NSC), as well as using an iterative ordered subset-expectation maximization (OSEM) algorithm. Calculated attenuation correction was performed assuming uniform attenuation (mu = 0.096 cm(-1)) for brain tissues when data are precorrected for scatter. The broad-beam attenuation coefficient (mu = 0.06 cm(-1)) determined from phantom studies was applied to NSC images. The images were coregistered and normalized using the default [15O]-H2O template supplied with SPM99 and an [18F]-FDG template. A t statistic image for the contrast condition effect was then constructed. The contrast comparing SC to NSC images suggest that regional brain metabolic activity decreases significantly in the frontal gyri, in addition to the middle temporal and postcentral gyri. On the other hand, activity increases in the cerebellum, thalamus, insula, brainstem, temporal lobe, and the frontal cortex. No significant changes were detected when comparing images reconstructed using analytic and iterative algorithms. It is concluded that, for some cerebral areas, significant differences in [18F]-FDG distribution arise when images are reconstructed with and without explicit SC. This needs to be considered when interpreting [18F]-FDG 3D brain PET images after applying SC.