BACKGROUND: Local anesthetic agents may exert antioxidant properties in various models. The aim of this work was to compare the antioxidant properties of lidocaine, bupivacaine and ropivacaine using an in vitro model of human erythrocytes submitted to an oxidative stress. METHODS: Blood was obtained from healthy volunteers. After separation, erythrocytes were suspended in phosphate buffer. Oxidative stress was induced by incubation with 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). (1) Effects of four different concentrations (50, 100, 300 and 600 microg ml(-1)) of lidocaine, bupivacaine and ropivacaine were studied in absence or presence of AAPH (20 mM). Potassium efflux was assessed by flame photometry. (2) Effects of 50 and 600 microg ml(-1) of lidocaine, bupivacaine and ropivacaine on AAPH (50 mM) induced hemolysis were also studied. (3) The oxygen radical absorbing capacity of lidocaine, bupivacaine and ropivacaine at the four concentrations was evaluated by the analysis of the allophycocyanin fluorescence. RESULTS: In absence of AAPH, neither extracellular potassium nor hemolysis was noted. AAPH (20 mM) induced a significant increase in extracellular potassium that was reduced by all local anesthetic agents, with greater effects for lidocaine. AAPH-induced hemolysis was significantly decreased by all the local anesthetic agents at higher concentration, but only by lidocaine at 50 microg ml(-1). Finally, none of the local anesthetic agents modified the allophycocyanin fluorescence. CONCLUSION: In this model, lidocaine was proved more effective than bupivacaine and ropivacaine in protecting human erythrocytes submitted to an oxidative challenge. This was not due to a free radical scavenging effect.