Complex lesions on coronary arteriography are seen commonly in patients with unstable angina and have been considered to be evidence of ruptured plaque with or without thrombus. To investigate the cause of complex lesions the histologic findings in atherectomy-derived specimens in 111 patients were correlated with lesion morphologic appearance on coronary arteriography. Among 91 patients with complex lesions, 81.3% had thrombus and 57.1% had evidence of plaque rupture. Of 20 patients with smooth lesions, 15% had thrombus and 10% had plaque rupture on histologic evaluation (p<0.01). On clinical correlation in 86 (83.3%) patients unstable angina was associated with thrombus, or plaque rupture (63.3%), or both on histologic evaluation (p<0.001 compared with stable angina). Complex lesions not associated with thrombus or plaque rupture occurred mainly (83.3%) in patients with stable angina. Our findings support the concept that complex lesions are usually due to recent thrombus, plaque rupture, or both in patients with unstable coronary syndromes but may be due to remote plaque disruption in patients with stable angina.