Cadmium and lead are heavy metals that cause vascular lesions such as atherosclerosis and hypertension. Toxicity of cadmium and lead on the regulation of fibrinolysis by vascular-composing cells was investigated using a cell culture system. It was found that cadmium promotes the synthesis of plasminogen activator inhibitor-1 (PAI-1) whereas lead inhibits the synthesis of tissue plasminogen activator (t-PA) in vascular endothelial cells; consequently, both heavy metals reduced fibrinolytic activity in the liquid phase. The responses of endothelial cells to cadmium and lead were different from those to other heavy metals and the release of the fibrinolytic proteins from vascular smooth muscle cells and fibroblasts was perturbed by cadmium and lead in different manners. In conclusion, the present study showed that cadmium and lead exhibit their toxicity on fibrinolysis regulated by vascular cells in different manners among cell types and the individual cell types respond to cadmium and lead in different manners with respect to the release of fibrinolytic proteins.