H₂S has been recognized as a signaling molecule and mediator of inflammation. Here, we report the kinetics and mechanism of its reaction with the neutrophil oxidant hypochlorous acid. Stopped flow studies, carried out at high pH, showed this reaction to be extremely fast, with a second-order rate constant extrapolated to be 2 × 10⁹ M⁻¹ s⁻¹ at pH 7.4. The reaction produces polysulfides rather than polythionates and may represent a novel pathway for protein Cys-sulfhydration, a recently proposed mechanism for H₂S signaling.