We report the results of a pilot study of topical 5% 5-fluorouracil (FU) cream for the treatment of alopecia areata, an immunologically modulated disorder of hair growth. Patients with extensive (>50% scalp surface area involvement) alopecia areata that was refractory to previous treatments applied 5-FU to one side of their scalp twice daily for 3 to 6 months. In all, 9 patients enrolled, and 8 completed the study. No patient experienced measurable hair growth on the treated side. Only mild irritation was observed in a subset of patients with application of 5-FU to the nonphotodamaged scalp skin. Based on these results, we cannot recommend the use of topical 5-FU for treatment of alopecia areata without further evidence of therapeutic benefit.