To evaluate arachidonic acid-related immunoregulatory mechanisms during long-term persistent pestivirus infection, we measured plasma contents of leukotriene C4 (LTC4), prostaglandin D2 (PGD2) and their plasma fatty acid (FA) precursor, arachidonic acid (AA), in six lambs with congenital border disease (BD). Significantly elevated average plasma LTC4 during the first half year of life was associated with increased PDG2 when compared to uninfected control lambs. Significantly elevated total plasma esterified AA stores suggest an effective BDV-mediated prostenoid immunostimulation. However, at 1 yr old, prostenoid secretion had fallen to normal (LTC4) or below normal (PGD2) levels. In contrast, there remained significantly elevated plasma esterified AA, present as available substrate for formation of these anti-viral immunoregulatory agents. These results suggested that preventing mobilization of AA from lipid stores for effective immune responses may be a viral strategy of BD virus that is associated with long term border disease effects.