Polyunsaturated fatty acids can be oxygenated by P450 in different ways--by epoxidation, by hydroxylation of the omega-side chain, by allylic and bis-allylic hydroxylation and by hydroxylation with double bond migration. Major organs for these oxygenations are the liver and the kidney. P450 is an ubiquitous enzyme. It is therefore not surprising that some of these reactions have been found in other organs and tissues. Many observations indicate that P450 oxygenates arachidonic acid in vivo in man and in experimental animals. This is hardly surprising. omega-Oxidation was discovered in vivo 60 years ago. It was more unexpected that biological activities have been associated with many of the P450 metabolites of arachidonic acid, at least in pharmacological doses. Epoxygenase metabolites of arachidonic acid have attracted the largest interest. In their critical review on epoxygenase metabolism of arachidonic acid in 1989, Fitzpatrick and Murphy pointed out some major differences between the PGH synthase, the lipoxygenase and the P450 pathways of arachidonic acid metabolism. Their main points are still valid and have only to be modified slightly in the light of recent results. First, lipoxygenases show a marked regiospecificity and stereospecificity, while many P450 seem to lack this specificity. There are, however, P450 isozymes which catalyse stereospecific epoxidations or hydroxylations. Many hydroxylases and at least some epoxygenases also show regiospecificity, i.e. oxygenate only one double bond or one specific carbon of the fatty acid substrate. In addition, preference for arachidonic acid and eicosapentaenoic acid may occur in the sense that other fatty acids are oxygenated with less regiospecificity. A more important difference is that prostaglandins and leukotrienes affect specific and well characterised receptors in cell membranes, while receptors for epoxides of arachidonic acid or other P450 metabolites have not been characterised. Nevertheless, epoxides of arachidonic acid have been found to induce a large number of different pharmacological effects. In some systems, effects have been noted at pm concentrations which might conceivably be in the physiological concentration range of these epoxides, e.g. after release from phospholipids by phospholipase A2. An intriguing possibility is that the effects of [Ca]i on different ion channels might possibly explain their biological actions. In situations when pharmacological doses are used, metabolism to epoxyprostanoids or other interactions with PGH synthase could also be of importance. Finally, one report on a specific receptor for 14R,15S-EpETrE in mononuclear cell membranes has just been published.(ABSTRACT TRUNCATED AT 400 WORDS)