Jaundiced serum has been shown to increase vascular sensitivity to the pressor effect of catecholamines. To determine whether this effect is caused by decreased vascular production of the vasodilator prostacyclin, we compared the ability of normal and jaundiced human serum to promote prostacyclin production in rat aortic tissue. Vascular prostacyclin production was significantly decreased after incubation of aortic tissue with jaundiced serum as compared with normal serum. Because lipid peroxides can inhibit prostacyclin synthesis, the relation of lipid peroxides to prostacyclin production was examined. Compared with normal serum, jaundiced serum contained higher concentrations of lipid peroxides and lower levels of selenium, an essential component of glutathione peroxidase. Prostacyclin production correlated inversely with the lipid peroxide level and directly with selenium concentration. These data demonstrate that jaundiced serum is deficient in promoting vascular prostacyclin production in vitro, and that this effect is associated with high levels of serum lipid peroxides. These findings may explain the propensity of jaundiced serum to increase vascular sensitivity to catecholamines.