The effects of a clinical oral dose of elastase on aortic atheroma development were studied in 0.2% cholesterol-fed rabbits, with or without endothelial denudation, using a balloon catheter. Elastase slightly decreased the serum lipids, but there was no significant difference from the serum lipids in the control groups. However, elastase significantly reduced the surface involvement of Sudan IV-positive staining areas of the aortas in rabbits with and without endothelial injury. The effect of elastase on SMC proliferation stimulated by hypercholesterolemia (C-serum or C-plasma) was also investigated in ex vivo experiments. The cholesterol levels in the serum and plasma of the elastase group were not significantly different from those of the 0.5% cholesterol-fed control rabbits. Proliferation of aortic smooth muscle cells was stimulated in the control group, while such stimulation in the elastase group was significantly lower. Therefore, elastase may suppress the stimulation through plasma factors, hence a reduction in atheroma development would ensue.