The cause of 180-degree diametrical artifactual defects in clinical thallium-201 SPECT imaging was investigated using phantom simulation. This artifact was observed on SPECT images acquired with a "body contour" or "peanut" orbit. It was hypothesized that this artifact was caused by differences in spatial resolution that occur when the heart-to-detector distance changes employing noncircular orbits. To test this hypothesis, a series of planar static images of a normal cylindrical phantom was obtained at varying distances from the camera detector head. From these images, tomographic acquisition files were created that simulated tomographic data acquired with circular orbits and elliptical orbits. The reconstructed phantom short-axis slices showed no artifacts for circular orbits. However, for various elliptical orbits, significant regional nonuniformity, similar to the artifacts noted in patients, was observed. The degree of nonuniformity correlated with the long-short axis ratio of elliptical orbits (r = 0.98). In addition, circular orbits with the phantom in an eccentric position resulted in similar nonuniformities. It is concluded that a noncircular tomographic orbit can create characteristic artifacts on thallium-201 SPECT images. For rotational thallium 201 SPECT, a circular orbit with the heart in the center of rotation should be employed.