markedly amplify clot lysis. The combination of RWR and a plasminogen activator increases the potency (for 50% lysis) of streptokinase, urokinase, and t-PA by 20-80-fold yet does not appear to increase nonspecific consumption of fibrinogen in vitro.3The following in vivo experiments were performed to test whether selective inhibition of fibrin-crosslinked a2-antiplasmin is an effective thrombolytic strategy. We used the rabbit jugular vein thrombolytic model originally described by Collen et a15 as it has been modified by our laboratory.6 The results suggest that specific inhibition of clot-bound a2-antiplasmin can significantly increase the rate of thrombolysis without increasing the consumption of clotting factors such as fibrinogen.Methods Proteins t-PA with a specific activity of 580,000 IU/mg was purchased from Genentech, South San Francisco, California. MAb RWR and MAb 40-160 (an antidigoxin, control antibody) were raised as described.3'7 Both MAbs were purified from ascites by ammonium sulfate precipitation followed by ion exchange chromatography on DEAE-Affigel Blue, Bio-Rad, Richmond, California. The concentration of MAb RWR was determined by a competition radioimmunoassay similar to that described by Mariani et al.8 The concentration of antidigoxin MAb 40-160 was measured by spectrophotometry with an extinction coefficient (1% solution, 1 cm path length) of 1.43.