Clinical specular microscopy was performed during acute rejection episodes in 20 patients. The following five distinct morphologic changes were noted: (1) "blackout" areas due to deposition of wandering cells on the endothelial layer, (2) intracytoplasmic blackout areas of unknown cause, (3) intracellular "bright" oval bodies related to the cell nucleus, (4) prominent variation in cell size, and (5) a sharp demarcation line of affected endothelial cells in a linear-type rejection. These morphologic changes were severe even in early rejection, and there was frequent persistence after the rejection episode was considered controlled by slit-lamp examination. Although these changes were not pathognomonic for endothelial rejection and could be seen in isolation in idiopathic uveitis and normal corneal transplant endothelium, a constellation of all these changes appeared specific for endothelial rejection.