The present investigation was coducted to examine the role of endogenous prostaglandin (PG) on blood flow and arenergic responses in the paw vasculature perfused without a pump. The PG precursors, arachidonic acid and dihomo-gamma-linolenic acid, given i.a. caused only small increments in paw blood flow which were much less than that caused by PGE2 and PGE1. The i.a. administration of the PG synthesis inhibitors, indomethacin, meclofenamate and naproxen, caused a decrease in paw blood flow and increase in vascular resistance, whereas eicosa-5,8,11,14-tetraynoic acid had no significant effect. Vasoconstrictor responses evoked by norepinerphrine were unaffected after administration of indomethacin or eicosa-5,8,11,14-tetraynoic acid, whereas slight potentiation of the response to sympathetic nerve stimulation was obtained after indomethacin. These results suggest that in the cutaneous vascular bed of the paw, endogenous PG decreases the vascular resitance, but plays only a minor adrenergic modulating role, and then only on the response to adrenergic nerve stimulation.