Current theories of idiopathic epiretinal membrane (ERM) pathogenesis, based mainly on clinical and autopsy studies, emphasize a glial tissue origin. The clinical and ultrastructural features of 101 cases of idiopathic ERMs removed from the macular area during vitrectomy were studied. The predominant cell type was retinal pigment epithelium (RPE) in 51 cases, fibrous astrocytes in 29 cases, fibrocytes in 14 cases, and myofibroblasts in 7 cases. Features of myofibroblastic differentiation were present in 64 cases. Myofibrocytes were more common in younger patients with shorter duration of symptoms. Fibrous astrocytes were more common in females. The high incidence of RPE cells in this series raises new questions regarding the pathogenesis of idiopathic ERMs.