The glycosaminoglycan (GAG) composition of a number of large and medium-sized arteries was studied in 6 alloxan-diabetic beagles and was compared with 6 normal, age-matched controls. Diabetic animals were maintained on diet and insulin for 100 days. The aortic arch, thoracic and abdominal segments, external iliac, superior mesenteric, renal, common carotid and coronary arteries were analyzed for hyaluronic acid (HA) and for heparan (HS), dermatan (DS), and chondroitin (CS) sulphates. All diabetic dogs displayed significant alterations. The HA content was reduced in iliac arteries, and together with HS, also in the thoracic aorta. HS or CS were increased in carotid, iliac and renal arteries, DS, a GAG constituent with very high affinity for low density lipoproteins, was significantly increased in coronary arteries alone. 2 additional animals which are excluded from this series did not become diabetic after alloxanization and showed no change in arterial GAG content. Early changes in the chemistry of the arterial ground substance seem to provide a clue to the precocious development of atherosclerotic disease in diabetes.