Peroxynitrite (the physiological mixture of ONOOH and its anion, ONOO − ) is a powerful biologically-relevant oxidant capable of oxidizing and damaging a range of important targets including sulfides, thiols, lipids, proteins, carbohydrates and nucleic acids. Excessive production of peroxynitrite is associated with several human pathologies including cardiovascular disease, ischemic-reperfusion injury, circulatory shock, inflammation and neurodegeneration. This study demonstrates that low-molecular-mass selenols (RSeH), selenides (RSeR') and to a lesser extent diselenides (RSeSeR') react with peroxynitrite with high rate constants. Low molecular mass selenols react particularly rapidly with peroxynitrite, with second order rate constants k 2 in the range 5.1×10 5 –1.9×10 6 M −1 s −1 , and 250–830 fold faster than the corresponding thiols (RSH) and many other endogenous biological targets. Reactions of peroxynitrite with selenides, including selenosugars are approximately 15-fold faster than their sulfur homologs with k 2 approximately 2.5×10 3 M −1 s −1 . The rate constants for diselenides and sulfides were slower with k 2 0.72–1.3×10 3 M −1 s −1 and approximately 2.1×10 2 M −1 s −1 respectively. These studies demonstrate that both endogenous and exogenous selenium-containing compounds may modulate peroxynitrite-mediated damage at sites of acute and chronic inflammation, with this being of particular relevance at extracellular sites where the thiol pool is limited. [ABSTRACT FROM AUTHOR]