Anti-oxidant actions of oxymethazoline and xylomethazoline were investigated by measuring inhibition of microsomal lipid peroxidation and hydroxyl radical scavenging activity. Oxymethazoline was shown to be a potent inhibitor of lipid peroxidation (IC 5 0 = 4.9 μM at t = 15 min, IC 5 0 = 8.1 μM at t = 30 min), in contrast to xylomethazoline. Both compounds were excellent hydroxyl radical scavengers. Their rate constants (k s = 1.1 x 10 1 2 M - 1 s - 1 for oxymethazoline andk s = 4.7 x 10 1 0 M - 1 s - 1 for xylomethazoline) exceeded the rate constant of a known powerful scavenger cimetidine (k s = 1.8 x 10 1 0 M - 1 s - 1 ). The difference in inhibiting lipid peroxidation might be explained by the fact that only oxymethazoline has a hydroxy group which can donate a hydrogen atom and terminate the chain reaction of lipid peroxidation. The mechanism of hydroxyl radical scavenging activity is still unclear. Moreover oxymethazoline seems to have a different mode of action in scavenging hydroxyl radicals than xylomethazoline and cimetidine which results in an extremely high rate constant. Because oxidants play a role in tissue damage in inflammation, it was hypothesized that especially oxymethazoline and to a lesser extent xylomethazoline may have an additional beneficial effect, due to their anti-oxidant properties, in the topical treatment of nasal inflammation.