OBJECTIVE Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in vitro, in tissue homogenates in a concentration-dependent manner, the concentration of 400 µg/ml demonstrating the most efficient lipid damaging effect . Both melatonin and its precursor, N-acetylserotonin, must possess antioxidant activities, both in vivo or in vitro, however, following some claims, N-acetylserotonin is a more effective extra- and intracellular antioxidant than melatonin. The aim of our study was to compare the effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro. METHODS Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were measured as the indices of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and N-acetylserotonin were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration level of 400 µg/ml. RESULTS In all the examined tissues, LPS stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS-stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was higher than that of melatonin. CONCLUSIONS The results of the reported study clearly indicate that N-acetylserotonin is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances.