This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and infravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to 1MB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.