Background: Topical 5-fluorouracil (5-FU) is effective in removing actinic keratoses but causes unsightly and painful erosions. Intermittent “pulse” 5-FU therapy has been described as being an effective and comfortable technique for destroying actinic keratoses. Objective: The purpose of this study was to determine the efficacy and cutaneous side effects of intermittent 5-FU therapy. Methods: Efficacy of treatment was evaluated by three experienced dermatologists separately comparing randomly arranged before and after photographs. Degree of skin reaction was graded from photographs taken during treatment. Results: Of 13 patients treated with intermittent 5-FU, two had an excellent result, three a good result, but eight failed to show discernible improvement. Efficacy was linked to the degree of skin irritation. Conclusion: Pulse 5-FU failed to clear actinic keratoses in most patients. Intermittent 5-FU treatment does not dissociate its therapeutic efficacy from its undesirable erosive effects. Pulse therapy is a less intensive way of employing 5-FU and may be of value in patients unwilling to accept the erosions and discomfort that accompany the traditional course of daily 5-FU applications. (J Am Acad Dermatol 1998;38:77-80.)