To define the factors important in photoreceptor cell morphogenesis, we have examined the ability of rods to extend neurites in vitro. Retinas from neonatal rats were dissociated and plated onto substrate-bound extracellular matrix (ECM) components or cell monolayers. When rods, identified with monoclonal antibodies to opsin, were in contact exclusively with purified ECM (e.g., laminin, fibronectin, type I collagen, or Matrigel), neurite outgrowth was extremely limited. By contrast, rods extended long neurites on Muller cells. Retinal or brain astrocytes, endothelial cells, 3T3 fibroblasts, or other retinal neurons were less supportive of rod process outgrowth. These data demonstrate regional specificity in the promotion of neurite outgrowth by glia and suggest that not all neurons within the retina require the same morphogenic factors.