Summary In peripheral lymphoid organs tbe number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including tbe control of lymphocyte migration by selective lymphocyte-higb endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune {MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Aracbidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not bave any effects on lympbocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on tbe role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.