Myocardial contrast echocardiography (MCE) has been used successfully during cardiac catheterization to assess regional perfusion in patients with coronary artery disease (CAD), although heterogeneity on MCE has been observed without underlying CAD. This study was undertaken to assess regional perfusion patterns on visual assessment of MCE when interpreted without knowledge of coronary anatomy, and to define potential sources of contrast heterogeneity not related to underlying CAD. Forty patients underwent intracoronary or aortic root MCE, or both, with use of 5% sonicated human serum albumin (Albunex) at the time of left heart catheterization. A single observer without knowledge of angiographic coronary anatomy reviewed all contrast echocardiographic studies for evidence of heterogeneous or collateral-dependent perfusion that was believed to be predictive of CAD. Of 110 vessels with paired echocardiographic and quantitative coronary angiographic data, 10 had lesions with > 70% luminal diameter stenosis and 6 of these were occluded. Of 100 vessels without significant stenosis, blinded analysis of MCE identified 36 regions with abnormal contrast considered predictive of CAD (false-positive results). False-positive studies occurred most often (incidence 46%) in the distribution of the left circumflex artery. Myocardial contrast in a coronary perfusion territory was completely absent after > or = 1 injection in 56 of 100 vessels without significant disease, although contrast was visualized on a subsequent injection in 51 of 56 vessels (91%). The low prevalence of disease among the population studied precluded meaningful estimation of test sensitivity for the detection of CAD. However, regional contrast heterogeneity was frequently observed on MCE in the absence of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)