Release of arachidonic acid from membrane phospholipids is a limiting step in the synthesis of both cyclooxygenase products and lipoxygenase products. The direct effects of prostacyclin and some lipoxygenase products on renin release were studied using rat renal cortical slices. Prostacyclin, at concentrations of 10−5M, stimulated renin secretion, but this effect was short-lived. Leukotrienes or their precursor, 5-hydroperoxyeicosatetraenoic acid, did not affect basal renin release. In contrast, 10−9M 12-hydroperoxyeicosatetraenoic acid and 10−8M 12-hydroxyeicosatetraenoic acid were potent inhibitors of renin secretion. Similarly, 15-hydroperoxyeicosatetraenoic acid and its hydroxy derivative, 15-hydroxyeicosatetraenoic acid, at somewhat higher molar concentrations (10−6M) also reduced basal renin. These studies confirm prostacyclin as a potential renin secretagogue; however, its action in vitro is transient, probably because of its rapid degradation. Our studies provide new evidence that products of the 12-lipoxygenase and 15-lipoxygenase pathways, reported to be present in renal vascular tissue, are potent inhibitors of renin secretion and much more active on a molar basis on renin secretion than is prostacyclin. These studies suggest the potential presence of a dual system of stimulation and suppression that may regulate renin secretion in normal and clinical states.