To obtain data concerning the pathology of diabetic arteries, aortas from 23 patients with diabetes mellitus [9 with insulin-dependent diabetes mellitus (IDDM) and 14 with non-insulin-dependent diabetes mellitus (NIDDM)] were collected at autopsy together with aortas from sex- and age-matched nondiabetic persons. A histomorphometric study was performed blindly on antifibronectin PAP-stained sections to determine the distribution of fibronectin-containing space in the vessels. In both IDDM and nonIDDM groups a statistically significant increase of approximately 45% was seen in the amount of stainable material in the tunica media. The increase was not influenced by the presence or absence of overlying plaque. No differences were seen between diabetic and nondiabetic vessels in the tunica intima. The content of extractable fibronectin in intima-media preparations was measured. The samples were extracted sequentially with buffered saline, a heparin-urea solution, and finally collagenase digestion. Fibronectin measured in these extracts showed that statistically significantly more of this glycoprotein was found in vessels from diabetic persons compared with nondiabetic persons, when comparing areas of the vessels without macroscopical visible plaque. However, only among IDDM patients increased amounts were apparent in plaque areas. These results indicate that diabetic patients develop structural alterations in the connective tissue of their arteries, consistent with a hypothesis of a diabetic macroangiopathy.