Tissue culture studies show that cell survival and process outgrowth from retinal ganglion cells depend on the molecular composition of the substrates over which the neurites grow, and on diffusible factors present in the medium. Recent work has begun to show that at least some of these components might be interactive. Since the conditions in a culture dish, as well as the patterns of antigen expression on cells in vitro, can differ considerably from those encountered in vivo, it is important to design experiments in vivo that examine how growing neurites relate to their natural microenvironment. By the use of transplantation techniques, it has been possible to provide evidence for a comparable duality of substrate-dependent and target-derived controls of optic axon growth, which might provide insight into the normal developmental process.