Photon attenuation in tissues is the primary physical degrading factor limiting both visual qualitative interpretation and quantitative analysis capabilities of reconstructed Positron Emission Tomography (PET) images. This study investigates the implementation and applicability of transmission atlas-guided attenuation correction in cerebral 3D PET imaging, thus eliminating the need for acquisition of a measured transmission scan. Patient-specific attenuation map is derived by anatomic standardization through nonlinear warping of a stereotactic transmission template obtained by averaging 11 scans of normal subjects. This template is coregistered to a specially designed tracer-specific 18F-[FDG] template constructed by scanning 17 normal subjects in resting condition during tracer uptake in a dark room. This emission template is first coregistered and spatially normalized to preliminary PET images of subjects corrected for scatter and attenuation using an approximate calculated method. The resulting transformation matrices are recorded and re-applied to the transmission template. The derived attenuation map is then forward projected to generate attenuation correction factors to be used for correcting the subjects' PET data. Twelve cerebral clinical studies are used for evaluation of the developed attenuation correction technique as compared to the standard pre-injection measured transmission-based method used in clinical routine. Statistical Parametric Mapping (SPM2) analysis is used to assess significant differences between images obtained using both techniques. The subjective qualitative assessment shows no significant visual differences between atlas-guided and transmission-based attenuation correction methods. However, the quantitative voxel-based analysis comparing atlas-guided to transmission-based attenuation corrections suggest that regional brain metabolic activity increases significantly bilaterally in the superior frontal and precentral gyri, in addition to the left middle temporal gyrus and the left frontal lobe. Conversely, activity decreases in the corpus callosum in the left parasagittal region. A new non-uniform attenuation correction method is thus proposed, which is suitable for both research and clinical routine applications in 3D brain PET imaging on a transmissionless PET scanner or when a patient-specific transmission scan is not available.