We evaluated the ultrastructural features of seven surgically excised submacular neovascular membranes from seven patients with the ocular histoplasmosis syndrome. Excised neovascular membranes were composed of fibrovascular tissue interposed between Bruch's membrane and the retinal pigment epithelium. Cellular components present in the membranes included, in decreasing order of frequency, retinal pigment epithelium, vascular endothelium, photoreceptor cells, macrophages, erythrocytes, ghost erythrocytes, fibrocytes, myofibroblasts, glial cells, smooth-muscle cells, and lymphocytes. Extracellular constituents of the neovascular membranes included 20 to 25-nm collagen fibrils, fibrin, 10-nm collagen fibrils, and fragments of Bruch's membrane and choroid. Our findings are consistent with the concept that subretinal neovascular membranes in the ocular histoplasmosis syndrome represent a nonspecific healing response to a local stimulus or injury.