Deficit of collagen may be a precipitating cause of aneurysm formation and expansion. Specimens of aneurysmal wall were obtained from 11 patients who underwent aneurysmectomy. Comparison aortic specimens were obtained from five patients who underwent aortofemoral bypass for occlusive disease. Collagenase activity was determined on the particulate and soluble fractions by the liberation of L-leucine, with bovine collagen as the substrate. Collagenase activity was detectable in the abdominal aortic aneurysms (AAAs) but not in atherosclerotic aorta or fascia. Collagenase activity was restricted to the particulate fraction in patients with AAAs, and it correlated with aneurysm size. These data suggest that (1) endogenous collagenolytic activity may be responsible for aneurysmal expansion and rupture and that (2) this enzyme is localized in the aneurysmal wall and is inoperative in arteries affected by atherosclerosis.