We report the use of weekly intralesional fluorouracil for treatment of entire psoriatic papules and portions of larger psoriatic plaques. Eleven patients participated and responded, with an average of 4.2 cm² clearing about the injection site in the treated lesions, in comparison with no improvement in the control lesions. We injected 1 ml of fluorouracil (50 mg/ml) to form an intradermal wheal of about 0.8 cm². Each patient received one to three injections at 1- to 2-week intervals, with an average of two injections per patient. The earliest signs of improvement occurred at 2 weeks; maximum clearing was achieved usually about 4 weeks after treatment began. At 3-month follow-up, four of the nine patients who had favorable response to treatment remained substantially in remission. Toxic effects were limited to local hyperpigmentation in seven patients, slight irritation in two patients, and moderate irritation in one patient. No systemic toxic effects were shown. Weekly pulse doses of fluorouracil given intralesionally instead of topically can greatly speed up response to therapy and can produce similarly good results. Intralesional administration of fluorouracil is locally effective, is often of long-term benefit, and can be tolerated well.