Oxidative stress decreases the deformability of erythrocytes. Anti-oxidant measures may alleviate, pro-oxidative damage may augment this decrease. Melatonin is reported to exert both anti-oxidant and pro-oxidant properties on erythrocytes. The aim of the present study was to evaluate the effects of melatonin on erythrocyte deformability under oxidative stress conditions induced by the combination of hydrogen peroxide (20 mM) and sodium azide (100 mu M). Erythrocyte suspensions were incubated for 10 min with melatonin (1-1000 mu M) prior to oxidative stress. Erythrocyte deformability was measured by Laser-assisted Optical Rotational Cell Analyzer (LORCA). Lipid peroxidation was determined via malondialdehyde (MDA) measurements by HPLC. Melatonin alone did not change erythrocyte deformability. Oxidative stress alone decreased the deformability of erythrocytes by 25.8 +/- 3.1% (P < 0.05). Melatonin pre-treatment augmented the decrease in erythrocyte deformability but prevented lipid peroxidation. Melatonin (1 mu M) did not cause any additional effect on erythrocyte deformability. Higher concentrations (10-1000 mu M) further decreased deformability (P < 0.05). Erythrocytes exposed to oxidative stress had MDA levels of 116.3 +/- 14.3 mu mol/g Hb. Melatonin (1 mu M) slightly increased MDA levels, but 1000 mu M melatonin reduced it by 35% (P < 0.05). These findings indicate that melatonin exerts antioxidant effect on lipids. Deterioration of erythrocyte deformability may be due to a separate pro-oxidative action on proteins.