Anti-Hu is an autoantibody that recognizes an antigen (Hu) highly restricted to neuronal nuclei. In the developing rat brain all neurons and the germinal cell layer were anti-Hu positive. Ependyma and choroid plexus were positive only in the early stages of development. The strongest expression of Hu was seen in the most mature neurons. The transitory nature of Cajal-Retzius and subplate neurons was confirmed with the anti-Hu staining. Although the Hu is also expressed by neural cells other than neurons, the strongest staining of mature neurons could indicate that Hu plays a role in the process of neuronal differentiation.