BACKGROUND: False-negative interpretations of dobutamine stress echocardiography (DSE) may be associated with reduced wall stress. Using measurements of contraction, we sought whether these segments were actually ischemic but unrecognized or showed normal contraction. METHODS: We studied 48 patients (29 men; mean age 60 +/- 10 years) with normal regional function on the basis of standard qualitative interpretation of DSE. At coronary angiography within 6 months of DSE, 32 were identified as having true-negative and 16 as having false-negative results of DSE. Three apical views were used to measure regional function with color Doppler tissue, integrated backscatter, and strain rate imaging. Cyclic variation of integrated backscatter was measured in 16 segments, and strain rate and peak systolic strain was calculated in 6 walls at rest and peak stress. RESULTS: Segments with false-negative results of DSE were divided into 2 groups with and without low wall stress according to previously published cut-off values. Age, sex, left ventricular mass, left ventricular geometric pattern, and peak workload were not significantly different between patients with true- and false-negative results of DSE. Importantly, no significant differences in cyclic variation and strain parameters at rest and peak stress were found among segments with true- and false-negative results of DSE with and without low wall stress. Stenosis severity had no influence on cyclic variation and strain parameters at peak stress. CONCLUSIONS: False-negative results of DSE reflect lack of ischemia rather than underinterpretation of regional left ventricular function. Quantitative markers are unlikely to increase the sensitivity of DSE.