To determine whether ischemia in the exercising dog is associated with preservation of subepicardial thickening relative to subendocardial thickening, 10 dogs were chronically instrumented with circumflex artery flow probes, hydraulic occluders, and pairs of ultrasonic microcrystals for determination of wall thickness in the circumflex artery distribution. One pair of crystals spanned the entire ventricular wall (transmural), and the other spanned the outer half of the ventricular wall. Inner wall thickness was computed as the difference between transmural wall thickness and outer wall thickness. Dogs performed control treadmill exercise and exercise with a coronary stenosis that reduced circumflex artery flow to resting control levels. Percent systolic thickening at rest for the transmural, inner, and outer regions was 21.3 ± 11.8%, 35.5 ± 20.3%, and 10.3 ± 5.0% (mean ± SD), respectively. During exercise without stenosis, systolic thickening increased to 143 ± 37% of control for outer wall crystals and 137 ± 26% of control for the inner portion of the wall. During exercise, the addition of a coronary stenosis caused a reduction in thickening to 17.7 ± 28.5% of control for the outer wall and 40.1 ± 32.3% of control for the inner portion of the wall; these were not significantly different. In contrast, normalized inner wall blood flow during exercise with circumflex artery stenosis (25.0 ± 16.0%) was significantly less than for the outer portion of the wall (48.5 ± 20.9%). Further, there was a close relation between changes in inner wall thickening and inner wall blood flow (r = 0.84), whereas there was only a very weak relation between changes in outer wall blood flow and function (r = 0.62; p = 0.04). During ischemia in the exercising dog, outer wall thickening is depressed out of proportion to reductions in outer wall blood flow and is not preserved relative to inner wall thickening.