We have presented evidence from a broad range of chemical, cell biological, and in vivo studies showing that ·NO can mediate tissue-protective reactions during oxidant stress, as well as toxic and tissue prooxidant effects. One predominant factor that has been identified which influences ·NO being protective versus toxic is the relative rates of production and concentrations of ·NO and the more "traditional" family of reactive oxygen species, including O2·-, H2O2, ·OH, LO·, LOO·, and high valency complexes of iron. Also, since so many anti-neutrophil actions of ·NO have been described, it is likely that ·NO will serve a protective role in acute inflammatory reactions. One issue is certain - many new truths remain to be revealed, as we continue to develop our understanding of the toxicology of reactive oxygen- and nitrogen-containing species. © 1996 American Chemical Society.