Highly variable results have been described for the use of topical diphenylcyclopropenone (DPCP) in the treatment of alopecia areata (AA). We enrolled 41 patients in a prospective open clinical trial. Of these, 17 patients had either AA totalis (AAT) or AA universalis (AAU), and 24 had severe alopecia (> 50% scalp involvement). After sensitization with DPCP 2% in acetone, progressively higher concentrations were applied once a week for a period of 6-12 months. Of the 41 patients, 38 (16 with AAT or AAU and 22 with extensive AA) completed therapy. Significant hair regrowth was observed in 15 of the 38 patients (39.5%) at 6 months: 5 with AAT or AAU (31.25%) and 10 with extensive alopecia (45.4%). The above results were sustained in 66.6% of patients for a 12-month-follow up- period. In our study, topical immunotherapy with DPCP proved to be an effective treatment, with prolonged therapeutic results.