Previous works suggest the interesting possibility of an effect of heparin on vascular smooth muscle cell (SMC) replication and migration via a selective inhibition of the expression of t-PA and u-PA both of which may play major roles during intimal hyperplasia following endothelial injury. The present study was undertaken to evaluate in vitro the effect of heparin on the growth and migration of aortic SMC isolated from transgenic mice showing single inactivations of the t-PA and u-PA genes comparatively to SMC isolated from control mice. With regard to serum-induced proliferation and migration, all cell types showed similar responses. On control cells, heparin inhibited in a dose-dependent manner the expression of both t-PA and u-PA protein and mRNA. Heparin however, similarly affected the mitogenic and chemotactic activity of FCS for SMC isolated from control, t-PA or u-PA-deficient mice therefore showing that heparin inhibits FCS-induced SMC proliferation via mechanism(s) other than single inhibition of t-PA or u-PA expression by smooth muscle cells.