The deacetylation of histone proteins, catalyzed by histone deacetylases (HDACs), is a common epigenetic modification of chromatin, associated with gene silencing. Although HDAC inhibitors are used clinically to treat nervous system disorders, such as epilepsy, very little is known about the expression pattern of the HDACs in the central nervous system. Identifying the cell types and developmental stages that express HDAC1 and HDAC2 within the brain is important for determining the therapeutic mode of action of HDAC inhibitors, and evaluating potential side effects. Here, we examined the expression of HDAC1 and HDAC2 in the murine brain at multiple developmental ages. HDAC1 is expressed in neural stem cells/progenitors and glia. In contrast, HDAC2 is initiated in neural progenitors and is up‐regulated in post‐mitotic neuroblasts and neurons, but not in fully differentiated glia. These results identify key developmental stages of HDAC expression and suggest transitions of neural development that may utilize HDAC1 and/or HDAC2. Developmental Dynamics 237:2256–2267, 2008. © 2008 Wiley‐Liss, Inc.