A corneal button from a 17-year-old woman with clinically known herpes simplex stromal keratitis, which later perforated when she was off therapy, was examined. A viral culture from the corneal surface was negative. Light microscopy revealed both acute and chronic inflammation, with multinucleated giant cells at Des-cemet's membrane. Transmission electron microscopy revealed active lysosomal activity within the polymor-phonuclear leukocytes in areas of collagen degradation, and herpes simplex viral particles at various stages of development in keratocytes undergoing lysis. Immunoperoxidase staining showed HSV antigen present in epithelium adjacent to the ulceration. We believe that the pathogenesis of stromal edema and necrosis in HSV stromal keratitis is multifactorial and involves both active viral infection and the host response.