Hypochlorous acid (HOCl) reacts with nitrite (NO₂⁻) at a molar ratio of 1:1 yielding an equimolar amount of nitrate. The rate of this reaction follows the dissociation of hypochlorous acid and decreases with the increasing of pH from 4 to 10 as assayed by stopped-flow analysis, suggesting that HOCl, not hypochlorite, is the reactant. The second-order rate constant at pH 7.2, 25°C, was estimated as (7.4 ± 1.3) × 10³m⁻¹s⁻¹, a rate considerably higher than that of the Fenton reaction (42m⁻¹s⁻¹). In human low-density lipoproteins (LDL) the reaction led to a loss of β-carotene and α-tocopherol. The NO₂⁻/HOCl mixture initiated lipid peroxidation in LDL, whereas NO₂⁻or HOCl alone had only little effect. When LDL was added immediately after mixing of NO₂⁻with HOCl, no loss of antioxidants or accumulation of lipid peroxidation products was observed, suggesting that a short-lived reactive intermediate, previously postulated as nitryl chloride, is the reactive species. The mixture NO₂⁻/HOCl as well as peroxynitrite led to the formation of 3-nitrotyrosine in LDL as assayed using a monoclonal anti-nitrotyrosine antibody. Furthermore, incubation of J774.2 macrophage-like cells with LDL, pretreated with the NO₂⁻/HOCl mixture, led to increased cellular accumulation of cholesterol. Thus modification of LDL caused by the reaction of nitrite with HOCl contributes to the formation of cholesterol-rich cells, a key feature of the early atherosclerotic lesion.