Objective-To assess whether inotropic stress myocardial perfusion imaging, echocardiography, or a combination of the two could enhance the detection of multivessel disease, over and above clinical and exercise electrocardiographic data. Design-100 consecutive patients investigated by exercise electrocardiography and diagnostic coronary arteriography underwent simultaneous inotropic stress Tc99m sestamibi SPECT (MIBI) imaging and echocardiography. MIBI imaging and echocardiographic data were analysed using a 12 segment left ventricular model, and each segment was ascribed to a particular coronary artery territory. The presence of perfusion defects with MIBI imaging or of wall thickening abnormality with echocardiography in at least two coronary artery territories at peak stress was taken as diagnostic of multivessel disease. Arteriographic evidence of > 50% stenosis was considered significant. Results-56 patients had multivessel disease. The sensitivity of the combination of MIBI imaging and echocardiography for detecting this was greater than either MIBI imaging or echocardiography alone (82%, 68%, and 68%, respectively; p = 0.005). Clinical and exercise electrocardiographic variables gave an R 2 value of 18.2% for predicting multivessel disease. The addition of either MIBI imaging (R 2 = 29.2%; p = 0.002) or echocardiography (R 2 = 28.8%; p < 0.001) enhanced the detection of multivessel disease, and the inclusion of both had further incremental value (R 2 = 34.8%; p = 0.003). Age (p = 0.03), MIBI imaging (p = 0.007), and echocardiography (p = 0.001) were independent predictors of multivessel disease. Conclusions-The assessment of both myocardial perfusion and contractile function by simultaneous inotropic stress MIBI imaging and echocardiography optimises the non-invasive detection of multivessel disease. (Heart 1998;79:274-280)