Activation of programmed cell death has recently been suggested to be involved in the delayed neuronal death of CA1 hippocampal neurons after global ischemia based on protection offered by protein synthesis inhibitors. Here, we studied the effects of transcriptional (actinomycin D) and translational (cycloheximide and anisomycin) inhibitors on glutamate-induced neuronal death in cerebellar granule cell cultures. The effects of aurintricarboxylic acid, an endonuclease inhibitor, were studied as well. No protection against glutamate toxicity could be observed with any of these inhibitors. We also analyzed the genomic DNA of glutamate-treated cells on agarose gel electrophoresis. No DNA degradation could be observed after glutamate exposure. We conclude that glutamate-induced neuronal death does not exhibit the features of apoptosis in cultured granule cells.