Immunocytochemical analysis of human saccular aneurysms, commonly referred to as berry aneurysms, was performed on formalin-fixed, paraffin-embedded sections using monoclonal antibodies with single and double staining methods. Atherosclerotic lesions were detected in all aneurysms, which ranged in size from 2 mm to 3 cm in diameter. Changes consistent with the earliest stages of atherogenesis, so-called "fatty streaks," were not detected. In the smallest aneurysms, atherosclerotic lesions were characterized by diffuse intimal thickening composed predominantly of proliferating smooth muscle cells (SMC) with a small number of macrophages and lymphocytes. Large aneurysms had advanced atherosclerotic lesions with cellular infiltrates composed mostly of macrophages, more mature looking SMC and a greater number of lymphocytes. Major histocompatibility complex (MHC) class II expression was detected predominantly in macrophages in all aneurysms. Some SMC in advanced atherosclerotic lesions, but not in diffuse intimal thickening, had MHC class II immunoreactivity. A significant number of lymphocytes and NK cells were found at the site of aneurysmal rupture. The progression of atherosclerosis within the aneurysmal sac correlated positively with aneurysmal growth, and we speculate may have contributed to aneurysmal rupture. Some evidence also suggested a possible role of atherosclerosis in the formation of berry aneurysms.