The purpose of the study was to evaluate the splanchnic extraction of tissue plasminogen activator (t-PA) in normal healthy fasting subjects after the injection of recombinant t-PA (rt-PA; Actilyse). In nine healthy volunteers (five male, four female), 21-29 years of age, the concentration of t-PA was determined in plasma samples taken simultaneously from a femoral artery and a large liver vein after a bolus injection (5, 10 or 20 mg) of rt-PA. The splanchnic plasma flow rate, the plasma volume, and the splanchnic extraction fraction of t-PA were determined. After the rt-PA injection, the measured arterial concentration of t-PA decreased from 36 750 to 45 pmol/l for t-PA antigen and from 50 700 to 17 pmol/l for active t-PA. The splanchnic extraction fraction decreased from 0.95 to 0.02 for t-PA antigen and from 0.78 to 0.08 (n = 3) for active t-PA. The extraction fraction was proportional to the arterial concentration of t-PA when the arterial concentration of t-PA was above about 300 pmol/l (both t-PA antigen and active t-PA). The median splanchnic plasma flow rate was 911 ml/min (range, 651-1149 ml/min). In the individual subject, the splanchnic plasma flow rate remained constant during the experimental period. The main conclusion of the study is that the splanchnic clearance and extraction fraction of t-PA, following an injection of rt-PA in the resting fasting steady state, depends on the arterial concentration of t-PA. The higher the arterial concentration of t-PA, the higher the extraction fraction of t-PA.