The second-order rate constant for the reaction of ebselen with peroxynitrite (ONOO - ) is (2.0 ± 0.1) 10 6 M - 1 s - 1 at pH ≥ 8 and 25°C, 3-4 orders of magnitude higher than the rate constants observed for cysteine, ascorbate, or methionine. The activation energy is relatively low, 12.8 kJ/mol. This is the fastest reaction of peroxynitrite observed so far. It may allow Se-containing compounds to play a novel role in the defense against peroxynitrite, one of the important reactive species generated during inflammatory processes.