To determine the etiology of aortic wall dissection, a histopathological study of the aorta in 20 cases with dissecting aortic aneurysm (DA), 3 cases with Marfan syndrome and 3 cases with annulo-aortic ectasia (AAE) was performed. Controls consisted of 348 cases of normally-aging aorta. In cases with aortic wall dissection, the histopathological changes in the undissected media were also carefully examined. In Marfan syndrome and AAE, there was a marked accumulation of acid mucopolysaccharide (AMPS) and its distribution in the wall was diffuse in patients under 50 years old, resulting in changes in elastic fibers including fragmentation, elastolysis and reticulation. In contrast, DA was histopathologically characterized by zonal fibrosis and abnormally-dilated vessels in the aortic media. These lesions were found in 8 (40%) of the 20 DA cases. The remaining 12 cases also had increased vascularization and fragmentation of elastic fibers. This medial fibrosis and increased vascularization were particularly marked in older patients. Among the 3 diseased entities responsible for aortic wall dissection, DA differed distinctly from Marfan syndrome or AAE as to the amount and site of AMPS accumulation in the media as well as fibrosis and hypervascularity in the outer half of the aortic media. In conclusion, aortic wall dissection in younger patients may be etiologically associated with the increased AMPS accumulation in the aortic media which may always be accompanied by degeneration of elastic fibers in this study, however, in older patients zonal fibrosis and abnormal vessels developing in the media are responsible for the dissection.