Spectrin is a cytoskeletal protein considered to be a major component of intracellular cohesion. Using an in situ hybridization approach, we have investigated the developmental expression of the mRNA encoding the alpha-subunit of rat brain spectrins, from birth to adulthood. alpha-Subunit mRNA is detectable at birth, in brain areas with perinatal neurogenesis, such as the cerebral cortex, hippocampus, thalamus, and olfactory bulb. alpha-Brain-spectrin mRNA increases gradually during the first postnatal days to reach a plateau between the second and the third week of life. In the young adult brain, the level of alpha-brain spectrin mRNA decreased globally. This spacio-temporal distribution argues for the involvement of the mRNA in the synthesis of both the erythroid and non-erythroid brain spectrin isoforms. We have focused our attention on the hippocampal formation and the cerebellum. In both regions, in situ hybridization signal variations are superimposable with neuronal maturation gradients. This pattern of variation, coupled with the known interaction of brain spectrins with other cytoskeletal proteins, agrees with the notion that brain spectrins may be involved in neuronal differentiation by way of the cytoskeletal lattice organization.