A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain single-photon emission tomographic (SPET) perfusion images, and then to draw the proportional anatomical Talairach's grid on each axial SPET image. First, the AC-PC line was defined on SPET images from the linear regression of four internal landmarks (frontal pole of the brain, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPET position of AC and PC points on the AC-PC line was automatically determined from measurements made on hard copies of magnetic resonance (MR) images of the patients. Finally, a proportional Talairach's grid was automatically drawn on each axial SPET image. To assess the accuracy of localization of AC and PC points, co-registered technetium-99m hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used. The mean displacements between estimated points on SPET and true points on MRI (Deltax=sagittal, Deltay=frontal and Deltaz=axial displacement) were calculated. The mean displacements (in mm) were Deltax=-1.4+/-1.8, Deltay=-1.7+/-3.3 and Deltaz=-1. 1+/-2.5 for AC, and Deltax=-1.8+/-1.8, Deltay=0.3+/-3.2 and Deltaz=-1.3+/-2.7 for PC. These displacements represented an error of less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Intra- and inter-observer comparisons did not reveal significant differences in mean displacements. Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPET perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPET-MRI co-registration.