Ten patients completed a weekly pulse dosing regimen for topical 5-fluorouracil therapy for multiple facial actinic keratoses. The method cleared an average of 98% of the lesions, without the severe irritation usually caused by the conventional, daily dosing regimen. Nine patients described the therapy as comfortable. Local irritation was limited to erythema. None of the patients suffered disruption in their social or business lives because of altered appearance. Patients had an average of 6.7 weeks of treatment and applied the medication 1 to 2 days per week; significant remissions were achieved. The longest available follow-up is with six patients who at 9 months remained 86% clear of lesions. This new method offers a significant advance in topical 5-fluorouracil therapy by reducing irritation to an acceptable level while maintaining efficacy.