The origin and fate of complex coronary lesions. Complex irregular coronary artery stenoses, representing plaque rupture/thrombosis, are associated with the acute coronary syndromes. However, the natural history (origin and fate) of these lesions is not known. To examine this issue we studied 255 patients who had had two to four arteriograms within a mean interval of 2.6 +/- 1.7 years. Of 53 irregular lesions that had progressed on a later arteriogram, 35 (66%) originated from areas that were smooth and less than 50% in stenosis diameter. Of 44 irregular lesions on an earlier study, 10 (23%) became totally occluded, five (11%) progressed in severity (all remained irregular), 25 (57%) showed no change in severity (all remained irregular), and four (9%) regressed (two became smooth). Nine of the 10 lesions progressing to occlusion were greater than or equal to 95% stenosed on the earlier study. Only 2 of 44 lesions (5%) showed smoothing. These findings are in agreement with the concept that irregular lesions represent ruptured atherosclerotic plaques and demonstrate that they usually originate from mildly occlusive smooth plaques. Markedly narrowed irregular lesions (greater than or equal to 95% stenosis) frequently progress to occlusion. Irregular lesions less than 90% narrowed commonly remain angiographically stable, and irregular over several years. They were found rarely to evolve into smooth-walled plaques. 