The fatty acid oxygenase activity of mesothelial cells and its role in inflammatory and neoplastic diseases of the mesothelium have not been defined. Techniques permitting in vitro cultivation of human mesothelial cells shed into serous cavities have permitted analysis of their specific metabolic capacities. The principal products of incubations of cultured human mesothelial cells with polyunsaturated fatty acids were analyzed using high performance liquid chromatography on reversed-, straight-, and chiral-phase columns and gas-liquid chromatography/mass spectrometry. The products included 6-keto-PGF1 alpha, 15-hydroxyeicosatetraenoic acid (S/R = 3.5), 11-hydroxyeicosatetraenoic acid, and 12-hydroxyheptadecatrienoic acid from arachidonic acid; 9- and 13-hydroxyoctadecadienoic acids (molar ratio of 9/13-hydroxyoctadecadienoic acids = 3.5, S/R ratios = 0.3 and 2.8, respectively) from linoleic acid; and 12-hydroxyheptadecadienoic acid from homo-gamma-linolenic acid. These products are indicative of a cyclooxygenase whose activation in vivo may play a significant role in serosal cavity pathology.