The aim of the current study was (i) to examine the overlap in the pattern of glucocorticoid receptor (GR)‐mediated transcriptional responses between different neuronal substrates and (ii) to assess the nature of these responses by differentiating between primary and downstream GR‐responsive genes. For this purpose, nerve growth factor‐differentiated catecholaminergic PC12 cells were used in which endogenous GRs were activated briefly with a high dose of corticosterone followed by gene expression profiling 1 and 3 h afterwards using Affymetrix GeneChips. The results revealed a strikingly similar temporal pattern to that which was reported previously in hippocampus, with only down‐regulated genes 1 h after GR activation and the majority of genes up‐regulated 3 h after GR activation. Real‐time quantatitive PCR of transcripts in cycloheximide‐treated cells showed that all five GR‐responsive genes selected from the 1‐h time point were primary responsive, whereas all four GR‐responsive genes selected from the 3‐h time point were downstream responsive. At the level of individual genes, the overlap with the previously generated hippocampal data sets was small, illustrating the cell‐type specifity of GR‐mediated genomic responses. Finally, we identified a number of interesting genes, such as SWI/SNF, synaptosomal‐associated protein 25 and certain Rab proteins which may play a role in the effects of glucocorticoids on catecholaminergic neuronal functioning.