Hypochlorite (HOCl), the product of the activated myeloperoxidase/H(2)O(2)/chloride (MPO/H(2)O(2)/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 (H(2)S) - which has recently been identified as an endogenous vasorelaxant - to counteract the action of HOCl on LDL. The results show that H(2)S could inhibit the atherogenic modification of LDL induced by HOCl, as measured by apolipoprotein alterations. Beside its HOCl scavenging potential, H(2)S was found to inhibit MPO (one may speculate that this occurs via H(2)S/heme interaction) and destroy H(2)O(2). Thus, H(2)S may interfere with the reactants and reaction products of the activated MPO/H(2)O(2)/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.