Hypochlorite (HOCl), the product of the activated myeloperoxidase/H₂O₂/chloride (MPO/H₂O₂/Cl⁻ ) system is favored as a trigger of LDL modifications, which may play a pivotal role in early atherogenesis. As HOCl has been shown to react with thiol-containing compounds like glutathione and N-acetylcysteine protecting LDL from HOCl modification, we have tested the ability of hydrogen sulfide (H₂S)—which has recently been identified as an endogenous vasorelaxant—to counteract the action of HOCl on LDL. The results show that H₂S could inhibit the atherogenic modification of LDL induced by HOCl, as measured by apolipoprotein alterations. Beside its HOCl scavenging potential, H₂S was found to inhibit MPO (one may speculate that this occurs via H₂S/heme interaction) and destroy H₂O₂. Thus, H₂S may interfere with the reactants and reaction products of the activated MPO/H₂O₂/Cl⁻ system. Our data add to the evidence of an anti-atherosclerotic action of this gasotransmitter taking the role of HOCl in the atherogenic modification of LDL into account.