During optic fiber regeneration in the goldfish, astrocytes in the visual system undergo a number of changes. These include hypertrophy of cell processes, increased reactivity with anti-intermediate filament antisera, and expression of cytoskeletal antigens not usually seen in these cells. In the present study, I have asked how much of this response might be due to interactions of glial cells with regenerating optic axons. Animals with and without a retina (regenerating and nonregenerating animals, respectively) had their optic nerve crushed and were then examined at various postoperative times with immunohistochemical methods. Three major differences between these two groups of animals were observed. First, in nonregenerating animals the crush lesion is not repopulated by immunoreactive glial cells while in regenerating animals it is. Second, the nature of the glial hypertrophy in the optic nerve is different in regenerating and nonregenerating animals. Finally, there is marked submeningeal swelling in regenerating nerves that is absent from nonregenerating nerves. Thus, these three aspects of the cellular response to optic nerve crush in the goldfish--wound healing, optic nerve gliosis, and non-neural cellular responses--appear to depend on interactions between regenerating optic axons and astrocytes or other non-neuronal cells of the visual paths for their expression.