Abstract Purpose To investigate the effects of oxygen tension on prostanoid synthesis in rabbit penile corpus cavernosum tissue (RCC) in organ culture. Materials and Methods Strips of rabbit corpus cavernosum were incubated in organ culture media under varying oxygen conditions (0 percent, 12 percent and 21 percent oxygen), in the presence or absence of acetylcholine and arachidonate stimulation. Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and mRNA PGHS expression were measured under both 0 percent and 21 percent oxygen conditions. Results Basal and acetylcholine-stimulated PGI 2 release was progressively diminished as a function of diminishing oxygen tension (pO 2 from approximately 165 to 25 mm.Hg). The basal and stimulated production of other prostanoids, thromboxane A 2, PGF 2 alpha and PGE 2, was also significantly inhibited under 0 percent oxygen (approximately 25 mm.Hg) conditions. However, incubation under 0 percent oxygen did not alter PGHS protein levels nor mRNA PGHS expression. Cavernosal strips incubated under 0 percent oxygen but supplemented with exogenous arachidonate (10 micromolar) maintained significantly lower PGI 2 production than tissues exposed to 21 percent oxygen (approximately 165 mm.Hg). Conclusions These data demonstrate that oxygen tension regulates prostaglandin production in corporal tissue. The reduction in prostanoid production during hypoxia can be attributed to inhibition of PGHS activity rather than the expression of the enzyme. In view of the role of PGI 2 as an inhibitor of platelet aggregation and white cell-endothelial adhesion, our findings may provide mechanistic insight into the alteration in corporal blood homeostasis during ischemic-hypoxic priapism.