A new cause of artifactual 201Tl defects on single photon emission computed tomography (SPECT) termed "upward creep" of the heart is described. In 102 consecutive patients undergoing 201Tl SPECT, 30 (29%) demonstrated upward creep defined by an upward movement of the heart of greater than or equal to 2 pixels during acquisition. In 45 consecutive patients with a less than 5% likelihood of coronary artery disease, 17 (38%) had upward creep. Of these nine had reversible 201Tl defects localized to the inferior and basal inferoseptal walls, while none of the 28 without upward creep had defects. The 17 low likelihood patients with upward creep had longer exercise duration and higher peak heart rate than those without upward creep. In five additional low likelihood patients with upward creep in whom imaging was immediately repeated, the upward creep pattern disappeared on the repeated images. After we changed our test protocol to begin imaging 15 min postexercise, only five (14%) of 36 low likelihood patients tested demonstrated upward creep. Upward creep is probably related to a transient increase in mean total lung volume early following exhaustive exercise, resulting in a mean lower position of the diaphragm (and thus the heart) at the beginning of imaging. The frequency of this source of false-positive 201Tl studies can be reduced by delaying SPECT acquisition until 15 min postexercise.