Surgical excision of subfoveal neovascular membranes may result in recovery of excellent visual acuity in patients with presumed ocular histoplasmosis but not in patients with age-related macular degeneration. To provide an explanation for this discrepancy, I analyzed the clinical and histopathologic findings in five patients with presumed ocular histoplasmosis. These findings provide evidence that the new vessels arising in the choroid in these patients usually grow within the subsensory retinal space and not in the subpigment epithelial space, as occurs in patients with age-related macular degeneration. In presumed ocular histoplasmosis, the new vessels are partly engulfed by a monolayer of proliferating retinal pigment epithelium. Surgical excision of this membrane permits reapproximation of the retinal receptors and native pigment epithelium and may be associated with remarkable return of visual acuity.