To determine whether focal changes in myocardial material properties are important in determining the response of first heart sound acceleration amplitude and frequency to myocardial ischemia, cardiac vibrations were simultaneously recorded from ischemic and nonischemic regions of canine epicardium by use of ultralight acceleration transducers. Cardiac acceleration and hemodynamics were recorded before and 5 min, 15 min, 1 h, and 2 h after left circumflex coronary artery occlusion. Peak-to-peak amplitude declined transiently in the nonischemic zone during early occlusion (P < 0.05) but was not decreased at any time in the ischemic myocardium. The median frequency of first heart sound vibrations in the ischemic region increased 31% within 5 min after occlusion (P < 0.01) and remained elevated for 2 h (P < 0.05). Nonischemic zone frequency was not statistically different from baseline at any time point. The disparate regional response of first heart sound vibrational frequency to myocardial ischemia suggests that propagating mechanical transients and myocardial contractile acceleration, rather than resonant vibrations, produce the first heart sound.