AbstractHerpes simplex virus (HSV) infection is a common cause of genital ulceration. Primary presentation is usually with multiple, small, discrete, tender ulcers. We report an unusual case of chronic, giant ulceration of the vulva in a woman immunosuppressed by the human immunodeficiency virus (HIV). This was the first presentation of symptomatic disease. The diagnosis of HSV infection was made initially on histological examination of a punch biopsy from the ulcer and subsequently confirmed by viral isolation. The response to antiviral therapy with acyclovir was rapid. Other causes of genital ulceration are discussed and we highlight the diagnostic benefit of histological examination of a punch biopsy.