Background: Dyshidrotic palmoplantar eczema is a frequent disease often running a chronic relapsing course. Topical glucocorticosteroids form the mainstay of therapy, and alternatives are urgently warranted. Objective: This study was performed to compare the efficacy of tacrolimus (FK506) 0.1% ointment and mometasone furoate 0.1% ointment in the treatment of dyshidrotic palmoplantar eczema. Methods: Sixteen patients were included in the study after a randomized, observer-blind, intrapersonal comparison protocol. After a 2-week washout period, the active treatment phase amounted to 4 weeks with twice-daily topical application of test substances and additional use of emollients at will. Thereafter, patients were monitored at weekly intervals up to 8 weeks. Results: The dyshidrotic area and severity index showed a more than 50% reduction of baseline values after 2 weeks of active treatment both for FK506 (P = .003) and mometasone furoate (P = .022) in palmar areas. After active treatment, a nonsignificant increase in the dyshidrotic area and severity index was seen with FK506 treated areas. Fourteen of 16 patients had recurring symptoms requiring further therapy within 3 weeks after the active treatment phase. Conclusion: Treatment with FK506 offers the possibility for rotational therapy with mometasone furoate in long-standing cases of chronic dyshidrotic palmar eczema. (J Am Acad Dermatol 2002;46:73-7.)