Abstract The topographic distribution of atherosclerotic lesions is influenced by biochemical factors intrinsic to the arterial wall. In the present work we have investigated whether the composition/chemical structure of glycosaminoglycans constitutes one of these factors. Normal human arteries were obtained at necropsy, and in order of decreasing susceptibility to atherosclerosis, consisted of the abdominal and thoracic aortas and the iliac and pulmonary arteries. The results showed similar concentrations of total glycosaminoglycan and collagen. Of the glycosaminoglycans known to interact with low-density lipoprotein (LDL), dermatan sulfate was present in all arteries in comparable concentrations, but the aortas had a 30% higher content of chondroitin 4/6-sulfate, which in turn was slightly enriched in 6-sulfated disaccharide units. LDLaffinity chromatography with dermatan sulfate+chondroitin 4/6-sulfate fractions demonstrated that increasing affinity to LDL matched an increasing susceptibility to atherosclerosis. Analysis of glycosaminoglycans in the eluates indicated a positive correlation between affinity to LDL and increasing molecular weight and the existence of a fraction of glycosaminoglycans of high affinity to LDL in the aortas only. These results suggest that arterial glycosaminoglycans participate in the multifactorial mechanisms that modulate the differential localization of atherosclerotic lesions.