In this prospective, open-label pilot study, we evaluated the safety and efficacy of etanercept, a TNF-alpha inhibitor, in the treatment of moderate to severe alopecia areata, alopecia totalis, or alopecia universalis. Seventeen otherwise healthy adults with moderate to severe alopecia areata were enrolled. The primary outcome measure was the extent of hair regrowth during and after the end of treatment as evaluated by the Severity of Alopecia Tool (the SALT score). After between 8 and 24 weeks of continuous treatment with etanercept 50 mg given subcutaneously twice weekly, significant regrowth of hair was not shown in any of the subjects treated. Based on these results, etanercept appears to be ineffective in treating subjects with treatment-refractory, moderate to severe alopecia areata, alopecia totalis, or alopecia universalis.