A 56-year-old man developed idiopathic corneal endotheliopathy. The lesion consisted of severe stromal edema at the lower half of the cornea along with a number of associated keratic precipitates and steadily progressed to the upper half of the cornea. By polymerase chain reaction, herpes simplex virus DNA was demonstrated in the aqueous humor of this patient. Corneal stromal edema was resolved in response to treatment with topically applied and systemic acyclovir. Herpes simplex virus DNA was repeatedly demonstrated in the aqueous humor when the endothelial lesion recurred later. This evidence strongly indicates that this unique endothelial disorder is of viral origin.