To our knowledge, no trial has so far been performed of 5-fluorouracil (5-FU) in the treatment of discoid lupus erythematosus. This open label study was carried out in 12 patients (5 males and 7 females, aged 20 to 47 years) to assess the short-and long-term efficacy and tolerability of a daily application of an ointment containing 5% 5-FU. The study was started in October 1993 when the disease was at a high degree of activity following summer sunlight exposure. After a 4-to 24-week treatment period, full remission was achieved in all patients. Healing resulted in cosmetically acceptable dyschromic and/or atrophic changes. During the summers 1994 and 1995, exacerbation of preexisting lesions and appearance of new lesions were observed in eight and two patients, respectively. However, remission of these lesions was obtained with a short course of therapy. The overall tolerability of the treatment was good or excellent in all patients. On the basis of the results of this preliminary study, topical 5-FU seems to be a promising therapeutic agent which might be introduced in the routine management of cutaneous lupus erythematosus.