Objective: To assess the efficacy of alefacept for the treatment of severe alopecia areata (AA). Design: Multicenter, double-blind, randomized, placebo-controlled clinical trial. Setting: Academic departments of dermatology in the United States. Participants: Forty-five individuals with chronic and severe AA affecting 50% to 95% of the scalp hair and resistant to previous therapies. Intervention: Alefacept, a US Food and Drug Administration-approved T-cell biologic inhibitor for the treatment of moderate to severe plaque psoriasis. Main Outcome Measure: Improved Severity of Alopecia Tool (SALT) score over 24 weeks. Results: Participants receiving alefacept for 12 consecutive weeks demonstrated no statistically significant improvement in AA when compared with a well-matched placebo-receiving group (P=.70). Conclusion: Alefacept is ineffective for the treatment of severe AA.