Our aim was to determine the amounts of eicosanoids in blood and synovial tissue of patients with knee arthrosis and to examine the effects of 2 doses of tepoxalin (50 mg twice, 200 mg twice), administered p.o. for 3.5 days. Concentrations of leukotriene B4 (LTB4, LTC4, and thromboxane B2 (TXB2) were measured in blood before and after oral administration of tepoxalin and release of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and LTC4 was measured in incubation media of synovial tissue, taken at surgery from patients treated with tepoxalin. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids. LT and TXB2 release was reduced by tepoxalin in both doses used. Under these conditions, PGE2, 6-keto-PGF1alpha, and LTC4 release from synovial tissue was detectable only after stimulation with calcium ionophore A23187. Washed synovial tissue, in which tepoxalin concentrations should be reduced, released higher amounts of all eicosanoids measured than directly incubated synovial tissue did. Pain after tepoxalin administration was significantly reduced. Relevant drug concentrations were detected in plasma and synovial fluid. Tepoxalin was well tolerated and had no marked adverse effects. At 400 mg, tepoxalin is a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) in blood and synovial tissue.