Long-term potentiation (LTP) in both area CA1 and the dentate gyrus is attenuated by stress and the evidence is consistent with the view that this is a consequence of increased activation of glucocorticoid receptors, in the hippocampus, following the stress-induced increase in circulating corticosterone. It has been shown that expression of the pro-inflammatory cytokine, interleukin-1beta (IL-1beta), is increased in hippocampus in response to stress; this finding together with the observation that IL-1beta exerts an inhibitory effect on LTP, suggests that IL-1beta may play a key role in mediating this inhibitory effect of stress on LTP. In this study, we explore this possibility and report that stress is also associated with increased reactive oxygen species production. The evidence presented supports the view that this is secondary to the stress-induced increase in IL-1beta concentration, as IL-1beta increased activity of superoxide dismutase and increased reactive oxygen species accumulation in hippocampus in vitro. We report that the inhibitory effect of stress on LTP is mimicked by H2O2, which increases reactive oxygen species accumulation, and by IL-1beta, the effect of which is overcome by the antioxidant, phenylarsine oxide. The hypothesis that the stress-induced increase in reactive oxygen species production may underlie the suppression of LTP is further supported by the finding that the effect of stress is abrogated by dietary manipulation with antioxidant vitamins E and C.