Experimental and theoretical investigation of the antioxidant activity of melatonin is carried out. The theoretical approach comprises the evaluation of several appropriate descriptors of scavenging activity with the help of quantum-chemistry methods. The values obtained are compared with available data for substances with established antioxidant properties. One of the most widely used markers for in vivo free radical oxidation processes is malondialdehyde (MDA) as an end product of membrane lipid peroxidation. Experimental support of the computed scavenging parameters is provided by estimation of the effect of supplementary melatonin therapy on the plasma levels of MDA in CRF patients on maintenance HD therapy. Different reaction paths have been considered and related to the obtained data, allowing speculations about the reaction mechanism and the antioxidant potential of melatonin for practical purposes.