Myocardial Doppler velocity (MDV) imaging may provide an objective correlate of ischemia, thereby reducing the expertise needed for interpreting stress echocardiography and improving its reproducibility. This study sought to independently validate the results of exercise MDV imaging with single-photon emission computed tomography (SPECT) perfusion imaging in 116 patients (age 60+/-12 years, 28 women) referred for exercise SPECT for diagnostic or prognostic assessment of coronary artery disease. Two-dimensional echocardiography was performed with simultaneous color MDV data acquisition before and after exercise treadmill testing. MDV data were processed off-line to display myocardial velocity profiles in each segment at rest and peak exercise. SPECT was analyzed using a 16-segment model and segments were classified as normal or showing resting or stress defects. Resting defects within segments showing normal function were attributed to attenuation. Color MDV data were compared with SPECT results, and a multivariate analysis (including exercise and SPECT results) was performed to identify the determinants of the exercise MDV response. Patients exercised maximally (peak rate-pressure product 27.6+/-6.1x10(3), and SPECT was abnormal in 33 patients. Of the 1,333 left ventricular segments evaluable by SPECT and MDV, 1,217 segments were classified as normal, 43 showed a stress defect, and 73 a rest defect. Segmental comparison of thallium findings and MDV showed that segments with a rest defect had a lower velocity at rest and stress than normal segments (p<0.001). Segments with a stress defect had a marked reduction in peak exercise velocity and less increment in velocity than normal segments. Heart rate, functional capacity, and presence of abnormally perfused segments were independent predictors of myocardial velocity at peak exercise. Thus, color MDV correlates with independent evidence of ischemia, although it is also influenced by exercise capacity and left ventricular function. This technique may permit a feasible approach to quantitation of exercise echocardiography.