The chicken optic system contains a brain-specific form of spectrin (alpha gamma-spectrin or fodrin) as a major membrane-associated, axonally transported cytoskeletal protein. We show here that the chicken optic system also contains an erythrocyte-specific form of spectrin (alpha beta' beta-spectrin), which has a more restricted distribution; it is confined to the plasma membrane of dendrites and cell bodies of retinal ganglion cells, is absent from the optic nerve fibers, and is not axonally transported from the retina into the optic nerve. During development of the optic system, the expression of alpha gamma-spectrin is constitutive in all cell types. On the other hand, the accumulation of alpha beta' beta-spectrin is detected in only the ganglion cells, and at a time in development which coincides with the phase of synaptogenesis. These results indicate the existence of a developmentally regulated mechanism that topologically segregates the erythroid and brain forms of spectrin from each other, and the former from axonal transport, and suggest that erythroid spectrin may be involved in establishing restricted membrane-cytoskeletal domains in neurons during synaptogenesis, and maintaining them in the adult cell.