A variety of prostaglandin synthetase inhibitors are cooxygenated during arachidonic acid peroxidation catalyzed by rat renal medulla prostaglandin synthetase or soybean lipoxygenase. Phenylbutazone, aminopyrine, 1,3-diphenylisobenzofuran, paracetamol, p-aminophenol, p-phenetidine and other o- and m-substituted aminophenol derivatives were cooxygenated, whereby prostaglandin synthetase inhibition was significantly weakened due to the formation of less inhibitory metabolites. In contrast, the inhibitory potency of diclofenac, indomethacin and phenacetin and its analogues remained unchanged during prostaglandin synthesis inhibition, because these compounds were no suitable cooxygenation substrates. Evidence is given that quinone imines may not be involved in the cooxidative metabolism of paracetamol and other aminophenols. As to the mechanisms of cooxygenation of suitable substrates dependent on their chemical structures either the arachidonic acid oxygenase or the subsequent hydroperoxidase reaction may trigger the oxygenation. 1,3-Diphenylisobenzofuran is metabolized during the formation of arachidonic acid hydroperoxides in contrast to paracetamol, which requires an additional peroxidase reaction to yield reactive metabolites.