The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes zoster infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy. Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications.