Seven cases of immune reactions against donor endothelium after penetrating keratoplasty were analyzed in a prospective study. Cell loss during the immune reaction period varied between 25% and 81% and seemed to continue thereafter, though much more slowly. The authors discuss the complex etiology of post-keratoplasty endothelial cell loss and make suggestions for the diagnosis and treatment of classic endothelial immune reactions with special reference to specular microscopy.