The configuration, time of onset, and duration of depressed ST segments during and after treadmill exercise testing were evaluated in 269 patients with angiographically proven coronary artery disease and 141 normal subjects. The test specificity was 93% and sensitivity 64%, the latter being influenced by the type of ST response; false-positive responses were rare with depressed, downsloping STs (1 of 123, 1%), occurred more frequently with horizontal ST depression (9 of 60, 15%), and occurred commonly with slowly upsloping STs (15 of 47, 32%). Depressed downsloping STs, ischemic changes appearing in the first 3 minutes of exercise, and those persisting past 8 minutes in recovery were associated with 91%, 86%, and 90% prevalences of two- to three-vessel or main left coronary disease, respectively. It is concluded that attention to configuration, time of onset, and duration of ischemic ST depression aids both in assessing the validity of exercise responses in diagnosing coronary artery disease and in delineating patients with advanced coronary obstruction.