Nitric oxide (.NO) can mediate tissue protective reactions during oxidant stress, as well as toxic and tissue prooxidant effects. Nitric oxide regulates critical lipid membrane and lipoprotein oxidation events, by 1) contributing to the formation of more potent secondary oxidants from superoxide (i.e. peroxynitrite) and 2) termination of lipid radicals to possibly less reactive secondary nitrogen-containing products (LONO, LOONO) which are in part organic peroxynitrites and are expected to be produced in vivo. Relative rates of production and steady state concentrations of superoxide and .NO and cellular sites of production will profoundly influence expression of the differential oxidant injury-enhancing and protective effects of .NO. Full understanding of the physiological roles of .NO, coupled with detailed insight into .NO regulation of oxygen radical-dependent reactions, will yield a more rational basis for the use of .NO donors for therapeutic purposes.