Topical mechlorethamine has been used in the treatment of mycosis fungoides for 20 years. The local use of other cytotoxic drugs has shown no advantages over mechlorethamine. A 0.02% solution (10 mg mechlorethamine in 50 ml of water) is mainly used due to its therapeutic efficacy with few side effects as compared with more concentrated solutions. Topical mechlorethamine is used daily at the beginning of the treatment until all lesions have cleared. Intralesional injections, are sometimes necessary. Weekly or twice-weekly applications are advisable as maintenance treatment. Long-standing remission have been obtained using that protocol of treatment. Side effects are pigmentation, local irritation and true sensitization (contact dermatitis). Only the latter makes it impossible to resume the treatment. Although sensitization to mechlorethamine has been used in the treatment of mycosis fungoides as a local immunotherapy, its efficacy is poor in that way as compared with its usual utilization. Attempts to desensitize patients to mechlorethamine have given poor results. The induction of a specific tolerance to mechlorethamine by intravenous injection prior to local application seems to be more promising. Results, however, are preliminary.