The proteasome is a large protease complex that recognizes, unfolds and degrades ubiquitinated proteins. Evidence is now accumulating that the ubiquitin-proteasome system may play an important role in neuronal apoptosis. However, little is known about the involvement of the proteasome in neuronal death in vivo, and there has been no prior analysis of the developmental expression of proteasome subunits in brain during periods of natural and inducible apoptotic death. We therefore studied the mRNA expression levels, using Northern analysis, of a subunit from each of the three key components of the proteasome in the rat mesencephalon from E21 through development and in adulthood. We measured mRNA expression for RC6 (a subunit of 20S), p112 (a subunit of 19S) and PA28-alpha (a subunit of 11S). The expression of PA28-alpha in rat mesencephalon was highest at the earliest times studied, and then decreased at PND 21, 28 and adult, in comparison to E21 (P<0.05) and PND 2, 4 and 7 (P<0.01). The expression of RC6 was lower in adult in comparison to PND 2, 4 and 21 (P<0.05) and PND 14 (P<0.01). There were no significant differences in the mRNA levels of p112 at various times studied. In situ hybridization at PND 7 indicated that all the subunits studied are particularly abundant in the SNpc. Thus, PA28-alpha and RC6 are developmentally regulated, and they may therefore play a role in developmental cell death or differentiation in neurons of the SN.