The multigenic program underlying neuronal apoptosis is mostly unknown. To study the program, we used genome-scale screening by oligonucleotide microarrays during serum and potassium deprivation-induced apoptosis of cerebellar granule neurons. From the 8740 genes interrogated by the arrays, 423 genes were found to be regulated at both the transcriptional and the posttranscriptional level and segregated into distinct clusters. Semantic clustering based on gene ontologies showed coordinated expression of genes with common biological functions and metabolic pathways. Among the genes implicated in apoptotic cerebellar granule neurons, 70 were in common with those differentially expressed in cortical neurons exposed to amyloid beta-protein, indicating the existence of common mechanisms responsible for neuronal cell death. Our results offer a genomic view of the changes that accompany neuronal apoptosis and yield new insights into the underlying molecular basis.