PrPc, a sialoglycoprotein present in the normal adult hamster brain, is particularly abundant in plastic brain regions but little is known about the level of expression and the localization of the protein during development. Western blot analysis of whole brain homogenates with mab3F4 show very low levels of the three main molecular weight forms of the protein at birth, in contrast to the strong and wide expression of mRNA transcripts. The PrPc levels increase sharply through P14 and are diminished somewhat in the adult. Regional analysis showed that in structures with ongoing growth or plasticity such as the olfactory bulb and hippocampus, PrPc remains high in the adult, while in areas where structural and functional relationships stabilize during development, such as the cortex and the thalamus, PrPc levels decline after the third postnatal week. In the neonate brain PrPc was prominent along fiber tracts similar to markers of axon elongation and in vitro experiments showed that the protein was present on the surface of elongating axons. PrPc is then localized to the synaptic neuropil in close spatio-temporal association with synapse formation. The localization of PrPc on elongating axons suggests a role for the protein in axon growth. In addition, the relative abundance of the protein in developing axon pathways and during synaptogenesis may provide a basis for the age-dependent susceptibility to transmissible spongiform encephalopathies.