To study its pharmacokinetics and especially microCi/100 mg was infused i.v. in 8 patients with a T-tube inserted in the common bile duct at choledocholithotomy 7-10 days prior to the study. Bile was collected in fractions by continuous suction over a 24 h period. Blood samples were taken and urine collected up to 48 h after the dose. Tolfenamic acid and its metabolites were separated by TLC and were quantitated by liquid scintillation counting. The pharmacokinetics of tolfenamic acid could be described by a two compartment open model with V1 of 3.67 +/- 0.681 and VSS of 8.0 +/- 1.01. The total plasma clearance of tolfenamic acid averaged 106 +/- 8 ml/min and t1/2 beta was 1.38 +/- 0.32 h. A three compartment open model was required to describe the kinetics of total 14C. The plasma clearance of total 14C was 15.4 +/- 3.9 ml/min and its terminal half life averaged 19.0 +/- 4.1 h. The long half-life was caused by the slow elimination of tolfenamic acid metabolites. Four metabolites were measured in plasma and bile. The principal metabolites in bile were glucuronide/sulphate conjugates of hydroxylated derivatives of tolfenamic acid. The recovery of tolfenamic acid in bile was 1.1 +/- 0.3% of the dose, whereas the recovery of total 14C was 18.6 +/- 4.9%. The biliary clearances of tolfenamic acid and total 14C were 1.2 +/- 0.3 and 5.0 +/- 2.1 ml/min, respectively. Thus, biliary excretion plays a considerable part in the pharmacokinetics of tolfenamic acid.