Absorption, distribution and elimination of the naturally occurring thrombin inhibitor hirudin were studied in dogs after intravenous and subcutaneous injection or intraduodenal application using an assay which detects the inhibitor in blood and urine by its antithrombin activity. The plasma concentration time curve after intravenous injection of the pure polypeptide could be best described by an open two-compartment model with first-order kinetics. Dependent on the dose, long-term infusion or subcutaneous injection produced anticoagulantly effective blood levels for a prolonged period of time. The enteral absorption is very low and does not suffice to produce adequate blood levels. Hirudin is distributed into the extracellular space and eliminated through the kidneys by glomerular filtration in active form with a half-time of about 1 h.