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Erythema multiforme is an acute mucocutaneous disorder, characterized by varying degrees of blistering and ulceration. We report a case of recurrent herpes-associated erythema multiforme managed with prophylactic acyclovir. An 11-year-old boy had lesions in the oral cavity and lips, which had been diagnosed as erythema multiforme minor. Four months later, the patient had desquamative gingivitis with erythematous lesions and necrotic areas in the skin. This episode was not related to drug intake, which suggests that the erythema multiforme was a result of herpetic infection. This hypothesis was supported by positive serology for herpes simplex virus. Five months later, the patient returned with new oral, skin and penis mucosal lesions. The diagnosis was confirmed as herpes simplex virus-associated erythema multiforme major. The episode was treated with acyclovir, and acyclovir was used prophylactically for 7 months to control the disease.