A preliminary report of a bilateral comparative study using fluorouracil (FU) topically on two patients with xeroderma pigmentosum is presented. The cutaneous reaction of the treated areas was similar to that seen during the treatment of actinic keratoses with FU. The treated areas of the two patients have remained free of lesions for 11 months while the untreated areas have continued to develop actinic keratoses and squamous cell carcinomas at a rate equal to the pretreatment period.