Basal (non-depolarized) and high K(+)-stimulated [3H]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 Ca(2+)-independent and was significantly increased following treatment with hydrogen peroxide (H2O2). On the other hand, depolarization-induced release had both a Ca(2+)-dependent and Ca(2+)-independent component. Both components of stimulated release were suppressed by H2O2. In fact, Ca(2+)-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.