Background Slow upsloping ST-segment depression during stress is thought to represent an ischemic response to exercise treadmill testing (ETT). Aim We used modern single-photon emission computed tomography (SPECT) imaging protocols to determine the incidence of ischemia in patients with slow upsloping ST depression during exercise and whether this response signifies more or less severe coronary artery disease (CAD) and risk in comparison with rapid upsloping ST depression and particularly with horizontal or downsloping ST depression. Methods We enrolled 33 patients (group 1) with rapid upsloping ST depression (>1 mm extending <0.08 seconds beyond J point), 32 patients (group 2) with slow upsloping depression (>1.5 mm extending >0.08 seconds beyond J point), and 35 patients (group 3) with horizontal or downsloping depression (>1 mm at 0.08 seconds beyond J point). Summed stress score (SSS), summed difference score (SDS), stress extent percent (SE%) and reversible extent percent (RE%) of perfusion abnormalities, lung-heart ratio (LHR), and transient ischemic dilatation (TID) were calculated. Results The mean SSS, SDS, SE%, RE%, and LHR were similar between groups 1 and 2 but significantly higher in group 3. Incidence of ischemia was similar in groups 1 and 2 (39% and 25%) but significantly higher in group 3 (77%, P <.001). Evidence of TID was seen in none of the patients in groups 1, in 3% of patients in group 2, and in 23% of patients in group 3. Conclusions Slow upsloping ST depression does not signify more severe ischemia, more extensive CAD, or more stress-induced backward left ventricular failure. Thus, it would be reasonable to consider patients with slow upsloping ST depression during exercise as having a very low likelihood of CAD, similar to patients with rapid upsloping ST depression. (Am Heart J 2002;143:482-7.)