The blood of 30 patients who received recombinant tissue-type plasminogen activator for lysis of acute coronary thrombosis was examined to identify the effects of this enzyme on the fibrinolytic and coagulation systems. Doses ranged from 20 to 80 mg and duration of infusion ranged from 15 minutes to 4.5 hours. Doses of 60 mg or less and duration of infusion of 2 hours or less caused only mild fibrinogenolysis, a 28% drop from baseline plasma fibrinogen concentrations to nadir. In contrast, higher doses or longer infusion periods led to significantly lower fibrinogen levels, a 61% decrease of fibrinogen levels at nadir (p less than 0.01), and this effect was sustained. Dosing by weight led to less appreciable fibrinogen breakdown. A strong negative correlation was seen between plasma plasminogen activator and fibrinogen levels (r = -0.83, p less than 0.001) during the infusion. In-vitro studies showed the enzyme to deplete fibrinogen rapidly, and this activation was blocked with a protease inhibitor.