Eight keratoplasty and 14 trabeculectomy specimens from Chandler's syndrome, Essential Iris Atrophy, and the Cogan-Reese syndrome were studied by electron microscopic and morphometric methods. The corneal endothelium in these conditions undergoes the most varied and complex alterations of any of the endotheliopathies so far studied. The size, shape, and density are altered, and the apical surface shows a myriad of abnormalities including alterations of the intercellular borders and junctions, and formation of numerous microvilli, filopodia, and "blebs." Whereas many cells have features indicative of metabolic activity, and others may have undergone division, still others appear to have been injured as they are disrupted and necrotic. There is also evidence for the presence of a low-grade, long-standing chronic inflammation and an associated loss of contact inhibition with formation of multiple endothelial layers. These changes do not encompass the entire endothelium, as some regions remain relatively unaffected, and each specimen presents a unique morphology. The endothelium is most affected in cases of Essential Iris Atrophy. Some changes may be related to such processes as cell migration and reparative activities. However, the presence of cell necrosis (apoptosis) and chronic inflammation (endotheliitis) may be more specifically related to the ICE syndrome endotheliopathy. The slit lamp and specular microscopy findings characteristic of this disease are correlated with the described histologic abnormalities.