In view of the paucity of information on the synovial-fluid pharmacokinetics of nonsteroidal anti-inflammatory drugs with a long half-life, we have compared the pharmacokinetics of tenoxicam (Tilcotil, Mobiflex) in plasma and synovial fluid in six patients with polyarthritis causing knee effusion. Plasma and synovial-fluid concentrations of tenoxicam were measured up to 96 h after an oral dose of a single 40 mg tablet. A full pharmacokinetic analysis was performed. Tenoxicam passed into synovial fluid attaining a peak concentration significantly later than that for plasma. However, the mean half-life for synovial fluid (45 h) was not significantly different from that for plasma (42 h). Comparison of area under the curve (AUC) indicated the total exposure of the synovial fluid to tenoxicam was consistent in different patients, comprising 50–60% of the corresponding plasma levels in every case. In the case of tenoxicam, synovial fluid exhibits the pharmacokinetic properties of a peripheral ‘tissue’ compartment.