OBJECTIVE To investigate the thrombolytic effects and the security of combined therapy of defibrinogenase (DEF) and lower dose urokinase (UK) on patients with acute myocardial infarction (AMI). METHODS Forty-five patients with AMI within 6 hours from the onset were divided into two groups, the combined therapy group (UK+DEF group, n=23) and the full dose UK group (UK group, n =22). The dosage of the UK in UK+DEF group was only the half of the full dos e UK group. In UK+DEF group, intravenous injection of 5 U DEF was preceded with intravenous infusion of UK, and after that, 5 U of DEF was infused intravenously in three separate times. Aspirin was prescribed for all patients. Coronary reperfusion was evaluated according to clinical criteria. The complication of bleeding was noted. Plasma fibrinogen (Fg) and D-dimer levels were determined before and after thrombolytic therapy. RESULTS The age, body weight, time from onset, reperfusion rate, reinfarction rate, bleeding complications and the mortality during hospitalization were similar in both groups (P>0.05), and no severe bleeding was found. The reperfusion rate of UK+DEF group (69.56 percent) was comparable with that of UK group (68.18 percent), P>0.05. While the time to reperfusion of UK+DEF group was markedly shorten than that of UK group, it was (62.08+/-32.40) minutes vs. (80.00+/-39.14) minutes respectively (P<0.01). The plasma levels of D-dimer were similar and were elevated at the 6 hours after the beginning of thrombolytic therapy both in two groups (P<0.05). The plasma Fg level was declined obviously in UK+DEF group with a decrease in 58.46 percent, while it was slightly declined in UK group with a 16.78 percent decrease in percentage compared to those levels of pre-thrombolysis. CONCLUSIONS The combination of DEF can enhance the thrombo lytic efficacy of UK, and can accelerate the lysis of coronary thrombus. The effect and the security of combination therapy are comparable to the full dose UK therapy.