To investigate whether direct oxidative damage may induce neuronal death via an apoptotic cell suicide pathway, we exposed cultured cortical neurons to the prooxidant hydrogen peroxide. Our experiments demonstrate that brief exposures to low concentrations of hydrogen peroxide can induce neuronal cell death via apoptosis as demonstrated by toxicity assays, specific DNA staining, and the appearance of DNA laddering on agarose gels. These results suggest that direct oxidative injury may serve as a general trigger for apoptosis in the CNS, and that other apoptotic stimuli, such as exposure to amyloid-beta peptides, may also involve oxidative injury. Peroxide-induced apoptosis may serve as a valuable model for further studies of apoptosis in neurons.