In 13 patients with psoriasis, fluorouracil at 5% concentration in ointment base was applied daily to psoriatic lesions under the occlusive dressings. The treated lesions became completely erosive at seven to nine trials, preceded by a burning sensation and accompanied by pain. A rapid epithelization was seen soon after stopping the fluorouracil treatment. Thus, all the patients showed a complete clearing of the lesions treated with the antimetabolite, and the psoriasis has not recurred during the observation period ranging from 6 to 13 months, except in a patient in whom small psoriatic lesions recurred after 11 months. The characteristic features of histological response of psoriatic lesions to fluorouracil was the destructive degeneration of the epidermal cells, mainly edema and vacuolated degeneration, leading to necrobiosis. No systemic toxicity was found in this series of patients.