Basal (non-depolarized) and high K+-stimulated [H-3]L-glutamate release in the presence and absence of Ca2+ were assessed using presynaptic nerve terminals (synaptosomes) isolated from the cerebral cortex of the guinea pig. Basal glutamate release was found to be Ca2+-independent and was significantly increased following treatment with hydrogen peroxide (H2O2). On the other hand, depolarization-induced release had both a Ca2+-dependent and Ca2+-independent component. Both components of stimulated release were suppressed by H2O2. In fact, Ca2+-dependent evoked release was virtually eliminated by H2O2 pretreatment. The data suggest that H2O2 exerts a differential effect on the neurochemical mechanisms involved in basal and stimulated glutamate release at the presynaptic nerve terminal.