The natural history and the factors determining the expansion of aneurysms have not been elucidated. To study the respective roles of elastolysis, collagenolysis, inflammatory cells, and hypertension in the pathogenesis of aneurysms, two previously described in vivo experimental models were used. An isolated segment of the abdominal aorta was infused with 15 units of pancreatic elastase. The maximal diameter of the aorta was measured before and after infusion and the isolated aorta was excised for classic histologic and immunohistologic studies. Twelve hours after the infusion of elastase the mean diameter of the aorta increased by 30%. The aorta had a cylindric form and only collagen fibers remained. Two and a half days after the infusion the aorta was spherical in shape and the diameter increased by 300% (3.09 +/- 0.08 mm) (p < 0.05). The entire aortic wall was invested by inflammatory cells. Six days after infusion the diameter increased by 421% (4.38 +/- 0.03 mm) (p < 0.05), and immunohistochemical staining showed numerous T lymphocytes and macrophages. Between 6 and 12 days, after perfusion inflammation decreased, the final diameter was 4.23 +/- 0.14 mm (not significant). Sixteen rats had thioglycollate and plasmin infusion, which are nonspecific activators of inflammation. Nine days after infusion the diameter of the aorta had increased by 288%; the elastic fibers of the media were fragmented and rare and the entire aortic wall was invaded by inflammatory cells, predominantly macrophages. The diameter of the aorta increased progressively. Two groups of 17 hypertensive rats (renovascular and spontaneous hypertension) received an aortic infusion of 15 units of pancreatic elastase. Elastolysis overlapped the limits of the infusion and inflammation persisted after 2 weeks. The mean diameter of the aorta (F = 11, p < 0.01) and the mean length of the aneurysms (F = 11.2, p < 0.001) were significantly increased. This study demonstrates that elastolysis and especially collagenolysis are determinants of aneurysmal expansion. Inflammation may be a promoting factor in the degradation of the aortic wall. Hypertension increases the hemodynamic stress to the aorta and activates mural inflammation.