The effects of prolonged intravenous administration of bovine milk xanthine oxidase (EC 1.2.3.2.) on blood lipids and arterial integrity were measured to determine if the administration of this enzyme produces metabolic changes conducive to plaque formation. New Zealand White rabbits were injected intravenously with bovine milk xanthine oxidase at 4-day intervals during a 13-week test period. At the end of the test period, the rabbits were killed and blood, heart, aorta, liver, and kidneys were collected and evaluated. Rabbits injected with phosphate buffer or acid-denatured xanthine oxidase for the same length of time served as negative controls. Additional rabbits fed a diet containing 3% added cholesterol for the same time period served as positive controls. The administration of xanthine oxidase in large amounts over a prolonged period did not alter serum cholesterol or triglyceride levels and did not reduce plasmalogen levels in the aorta or heart. Xanthine oxidase administration did not induce arterial plaque formation. Cholesterol feeding over the same time period increased serum cholesterol levels, reduced liver xanthine oxidase activity levels and resulted in a marked development of arterial plaques. Althouth xanthine oxidase activity was found in liver from all rabbits, enzyme activity was not detectable in aorta, heart or kidneys from any rabbit. Free or complexed bovine milk xanthine oxidase could not be demonstrated in heart, aorta, liver or kidneys from any of the rabbits with immunodiffusion or with immunofluorescent techniques. The study showed that when large intravenous doses of bovine milk xanthine oxidase were given to rabbits, the enzyme was not deposited in heart, aorta, liver or kidneys. The study also showed that large intravenous doses of xanthine oxidase over prolonged periods did not deplete arterial or coronary tissue plasmalogens, and did not induce arterial plaque formation.