Benzydamine [1-benzyl-3-(3-dimethylamino)propoxy-1H-indazole] is a drug with analgesic, anesthetic, antimicrobial and anti-inflammatory activity. The purpose of the present study was to investigate the effect of benzydamine on prostaglandin production in human gingival fibroblasts. Benzydamine significantly reduced the basal production of both prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha, the stable breakdown product of prostaglandin I2 (PGI2), in unstimulated human gingival fibroblasts. When the cells were treated simultaneously with benzydamine and the cytokines IL-1 beta or TNF alpha, the agent benzydamine reduced (P < 0.05) the stimulatory effect of IL-1 beta and TNF alpha respectively, on PGE2 and PGI2 production in human gingival fibroblasts. Furthermore, benzydamine reduced (P < 0.05) both the basal level and the cytokine-induced 3H-arachidonic acid release 3H-(AA) in gingival fibroblasts. The addition of exogenous arachidonic acid to the cells resulted in enhanced PGE2 production, which was reduced (P < 0.05) in the presence of benzydamine. The study indicates that benzydamine reduces the prostaglandin synthesis in gingival fibroblasts, partly at the level of phospholipase A2, by diminishing the liberation of arachidonic acid (AA) from phospholipids, and partly at the level of cyclooxygenase. The inhibitory effect of benzydamine on prostaglandin production may explain the anti-inflammatory effect of the drug in the management of patients with oral inflammatory conditions.