Eighty-six consecutive first grafts performed between 1980 and 1990 (86 patients) for herpes simplex keratitis (HSK) were studied retrospectively (mean follow-up 4.1 years). Indications for penetrating keratoplasty (PKP) included: persistent inflammation, descemetocele or perforation (21/86); stromal opacities with vascularization (43/86), and avascular stromal opacities (22/86). The overall survival rate of clear transplants was 80% after 2 and 68% after 11 years. Corneal inflammation at the time of surgery was found to be a prognostic factor, but not corneal vascularization: The 2-year survival rates for clear grafts were 95% for avascular and 83% for vascularized stromal opacities in clinically inactive eyes, as against 58% for clinically active corneas at the time of surgery. HSV-specific structural proteins were immunohistochemically detectable most often in keratectomy specimens from patients with corneal inflammation before the operation (91%). In the group of clinically inactive stromal opacities, HSV antigens were detectable significantly (P < 0.001, chi-square test) more often in keratectomy specimens from patients with avascular opacities than in those with vascularized opacities. This may explain why corneal vascularization is not a significant risk factor for HSV recurrences. The different frequency of HSV-specific proteins in avascular and vascularized corneas merits attention in the intra- and postoperative management of patients with HSK undergoing corneal transplantation.