BACKGROUND Mild oxidative stress induces the cells to proliferate. On the other hand, too much oxidative stress may cause cells to die or suffer irreversible damage. Cancer and beta-cells destruction on diabetes can illustrate the paradoxical roles of superoxide in the physiological cellular responses. METHODS The activation of resting human peripheral blood lymphocytes (HPBL) was done using different mitogens such as phytohemagglutinin (PHA), concanavalin A (ConA), and phorbol ester (PMA), as well the superoxide producing system, paraquat. The physiological responses were evaluated in terms of proliferation using MTT to assess activation of the resting cells, as well apoptosis and necrosis by fluorescent microscopy. RESULTS Our results show that the increase in oxidative status by superoxide in resting human peripheral blood lymphocytes induces cells to proliferate; however, higher concentrations of superoxide are harmful, inducing apoptosis and necrosis. CONCLUSIONS Our results clearly show the involvement of superoxide (supplied by paraquat and/or induced with mitogens) in physiological responses such as proliferation and apoptosis. Such divergent responses should be explained in terms of our dose-response observations.