The purpose of these experiments was to assess the role of the lipoxygenation products of arachidonic acid in hamster periodontitis. Phenidone and ketoconazole were used as inhibitors of leukotriene synthesis. In an established periodontitis, both drugs administered for 30 days induced a statistically significant decrease in PMNLs in the infiltrated connective tissue and around bacterial plaque within periodontal pockets. These changes were associated with a significant decrease in osteoclastic bone resorption. The results suggest that leukotrienes, and particularly leukotriene B4, are involved during hamster periodontitis and are responsible for PMNL infiltration of the periodontal pocket. The effects on bone are probably the consequence of the reduced inflammation resulting from the decrease in PMNL chemotaxis.