5, 8, 11, 14 eicosatetraynoic acid ("ETYA", Roche 3-1428) is a competitive inhibitor of arachidonic acid metabolism. It effectively inhibits the action of both the lipoxygenases and the fatty acid cyclooxygenases both of which utilize arachidonic acid as a substrate. In the present work, we have shown that ETYA stimulates luteinizing hormone (LH) release from cultured pituitary cells (ED50 = 10 micrograms/ml). Stimulation is not due to contaminants present in the preparation, since highly purified ETYA (characterized by GC-MS) stimulates release, while contaminants removed by silicic acid chromatography do not. In addition, neither oxidized solutions of ETYA nor arachidonic acid itself stimulate LH release. ETYA stimulated release is dose dependent and is inhibited by ions which antagonize Ca2+ action. The observation that neither indomethecin (10, 100 micrograms/ml) nor meclofenamate (1.0, 10 micrograms/ml) stimulate LH release suggests that the effect of ETYA cannot be explained by an action on cyclooxygenase. The action of ETYA may be mediated either via an effect on lipoxygenase or through some nonspecific action (such as altered membrane fluidity).