Tenoxicam and indomethacin were studied with regard to their effects to modulate mediator release (histamine, prostaglandin E2 (PGE2) mono-hydroxyeicosatetraenoic acids, leukotrienes) from various cells. For histamine release human lymphocytes, monocytes, and basophils were analyzed with either anti-IgE or the calcium ionophore A 23187. Rat mast cells were stimulated with the calcium ionophore A 23187. With tenoxicam significant inhibition of histamine release was obtained as compared to the effects of indomethacin. Enhancement of histamine release at defined concentrations was more often observed with indomethacin than with tenoxicam. At high concentrations of indomethacin the formation of the radiolabelled phospholipids and 5S-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (14C-arachidonic acid metabolites) from stimulated human polymorphonuclear neutrophilic leukocytes was inhibited. With regard to endogenous leukotriene and PGE2 release tenoxicam inhibited leukotrienes B4 and C4 and PGE2 release. Tenoxicam appeared to be more active than indomethacin.