The increased incidence of corneal graft failure in patients with herpes simplex virus (HSV) keratitis may be due in part to reactivation of latent HSV following surgical corneal trauma and postoperative corticosteroid therapy. To determine the onset, frequency, and nature of HSV recurrences following penetrating keratoplasty (PKP), 21 HSV type 1 (HSV-1) latently infected rabbits underwent unilateral autograft PKP. Opposite unoperated eyes served as HSV-1 latently infected controls. Corneal autografts were performed so that immunologic graft rejection would not be confused with recurrent HSV-1 stromal disease. After PKP, 11 of the 21 eyes were treated with dexamethasone. Ocular cultures and slit-lamp examinations were performed daily for the first postoperative 8 days and every other day thereafter for 82 days. Nine (82%) of the 11 dexamethasone-treated PKP eyes, 2 (20%) of the PKP eyes not treated with dexamethasone, and 3 (17%) of the 18 unoperated eyes had positive HSV-1 ocular cultures. Geographic ulcers appeared only in the PKP eyes treated with dexamethasone; 9 (82%) of the 11 PKP eyes treated with dexamethasone developed geographic ulcers. Between the 24th and 90th postoperative days, stromal keratitis appeared in 5 (56%) of the 9 PKP eyes treated with dexamethasone and in 2 (25%) of the 8 PKP eyes not treated with dexamethasone. Autograft PKP with postoperative corticosteroids significantly increased HSV-1 ocular shedding, epithelial ulceration, and stromal keratitis. This experimental model provides a useful tool to further investigate the development and treatment of HSV-1 epithelial and stromal recurrences after PKP.