Inflammatory cells often are seen in the walls of human aortic aneurysms, but their significance is uncertain. To investigate their actions an in vivo model of arterial aneurysms was developed in the rat. Fifteen units of hog pancreatic elastase were infused for 2 hours into the isolated abdominal aorta in 26 rats. The vessels were measured in vivo and were excised for conventional histologic and immunohistologic study at selected intervals. In untreated control rats the diameter of the aorta was 1.04 ± 0.02 mm. Immediately after infusion with elastase the aorta dilated 26% to 1.31 ± 0.02 mm (p = NS), with no histologically demonstrable remaining elastic lamellae. Two and one half days after infusion the aorta dilated nearly 300% to 3.09 ± 0.08 mm (p < 0.05). These vessels exhibited large numbers of activated macrophages and T cells in the media. Three and 4 days after infusion the vessels dilated 388% to 4.04 ± 0.09 mm and 367% to 3.82 ± 0.31 mm, respectively. These vessels also exhibited numerous inflammatory cells in the media. Six days after infusion the vessels enlarged 421% to 4.38 ± 0.03 mm (p < 0.05), and the infiltrate persisted staining immunohistologically for macrophages, polymorphic neutrophils, and T lymphocytes. Twelve days after infusion the aneurysms remained enlarged but stable at 4.23 ± 0.14 mm (p = NS). At this time the number of inflammatory cells regressed to control levels. The temporal correlation between inflammatory infiltrate and aneurysmal enlargement suggests that inflammatory cells may participate in the destruction of the aneurysmal vessel wall thereby promoting progressive enlargement. To further examine this hypothesis, the aortas in 16 additional rats were infused with thioglycolate plus plasmin. These agents are nonspecific activators of the immune system. Five days after infusion the untreated aorta enlarged 213% to 2.21 ± 0.23 mm (p < 0.05), with fragmentation of elastic lamellae and numerous activated macrophages in the wall. Nine days after infusion the inflammatory response persisted, and the aortas dilated 288% to 3.00 ± 0.28 mm (p < 0.05). These findings are consistent with the hypothesis that inflammatory cells may participate in the progressive or “secondary” enlargement of aneurysms. (J Vasc Surg 1992;16:139–47.)