The effects of arachidonic acid in cerebral blood vessels has been examined using rings of canine cerebral arteries. Arachidonic acid produced dose-dependent contractions of this preparation even after mechanical removal of the endothelium. The contractions were not blocked by indomethacin or acetylsalicylic acid, both of which inhibit cyclooxygenase, but were inhibited by nordihydroguaiaretic acid which is a lipoxygenase inhibitor, BW 755c which blocks both pathways, and FPL 55712 which is an antagonist at leukotriene receptors. These data imply that arachidonic acid-induced contractions are mediated by products of the lipoxygenase pathway. Leukotrienes and cyclooxygenase products are generated by this preparation as shown by HPLC and radioimmunoassay and both LTC4 and LTD4 produce contractions in cerebral arteries lending further evidence in support of this suggestion.