Using purified prostaglandin (PG) H synthase, which synthesizes PGG2 and PGH2 from arachidonic acid, we were able to assay for the presence of peroxide activators in biological tissues. This assay system, capable of detecting both hydrogen peroxide (H2O2) and lipid hydroperoxides, detected a significant amount of synthase activator in plasma. Treatment of the active preparations with catalase and glutathione peroxidase showed that the principal activator in normal human plasma was a lipid hydroperoxide rather than H2O2.