We and others reported that endothelial cells (ECs) convert linoleic acid into 13-hydroxyoctadecadienoic acid (13-H0DE) under basal conditions, and arachidonic acid into 15-hydroxyeicosatet-raenoic acid (15-HETE) following stimulation (1,2). We also reported that lipoxygenase metabolism influenced platelet (PLT) interactions with ECs, tumor cells (TCs) and extracellular matrix (BM) (1,3,4). Thus, we performed studies to determine i) if TCs also produce 13-H0DE and HETEs, and ii) the effect of TC and EC 13-H0DE and HETEs synthesis on TC/EC adhesion. We measured i) the ratios of 13-H0DE:HETE in 5TC lines, under basal and stimulated conditions, in metastatic and non-metastatic TCs of the same cell line, and TCs treated with salicylate (SAL) or dipyridamole (DIP), and ii) their relationships with TC adhesion to ECs and BM. 13-H0DE and HETEs were assayed by HPLC. TC adhesion was assayed as the # radiolabelled TCs adherent to ECs or BM. cAMP was assayed by RIA. Under basal conditions, TCs produced 13-H0DE and HETEs, the intracellular ratio of which markedly affected their adhesivity; e.g. the least adhesive TC (U87MG glioblastoma) produced 21Xs more 13-H0DE than HETE’s, while a more adhesive TC (A549, adenocarcinoma) produced 4Xs more HETEs than 13-H0DE. Non-metastatic TCs preferentially produced 13-H0DE while metastatic TCs of the same cell line, produced HETEs. Stimulation of TCs or ECs decreased 13-H0DE, and increased HETE synthesis and TC/EC adhesion. Inhibiting intracellular 13-H0DE synthesis in either TCs or EC (SAL RX) enhanced TC/EC and TC/BM adhesion. Enhancing 13-H0DE synthesis by elevating cAMP (DIP RX) inhibited TC/EC and TC/BM adhesion. We conclude that 1) in vitro TCs produce 13-H0DE and HETEs, 2) the ratio of 13-H0DE:HETEs in TCs and ECs affects their adhesivity; and 3) the ratio of intracellular 13-H0DE:HETEs depends upon cAMP. This suggests that 13-H0DE:HETE ratios in TCs and ECs influence the adhesion process in the pathogenesis of thrombosis and metastasis in vivo. (1) Buchanan et al, JBC 30:1985. (2) Hopkins et al, JBC 29:1984. (3) Bastida et al, Int. J. Cane. 1987. (4) Buchanan et al, Prost. Leuk. Med., 1986.