Background: A topical formulation of tacrolimus, an immunosuppressant currently marketed for the prevention of rejection after solid organ transplant, is a potential therapeutic agent for atopic dermatitis. Objective: We sought to determine the safety and efficacy of tacrolimus ointment in pediatric patients with moderate-to-severe atopic dermatitis. Methods: In this double-blind, vehicle-controlled multicenter trial, children ages 7 to 16 years were treated with twice daily application of tacrolimus ointment at 1 of 3 concentrations (0.03% [n = 43], 0.1% [n = 49], or 0.3% [n = 44]) or vehicle (n = 44) for up to 22 days, with a 2-week follow-up period. Results: The Physician’s Global Evaluation of clinical response showed that 69% (95% confidence interval: 53-82) of patients in the 0.03% tacrolimus ointment group, 67% (95% confidence interval: 52-81) in the 0.1% tacrolimus ointment group, and 70% (95% confidence interval: 54-83) in the 0.3% tacrolimus ointment group, compared with 38% (95% confidence interval: 24-54) in the vehicle group, had a marked to excellent (≥75%) improvement or clearing of their atopic dermatitis (P = .005, .007, and .004, respectively for the 3 tacrolimus groups compared with the vehicle group). The mean percent improvement for a modified Eczema Area and Severity Index at end of treatment for each of the 3 tacrolimus groups (0.03%, 72%; 0.1%, 77%; and 0.3%, 81%) was significantly better than that of the vehicle group (26%; P < .001). The median percent reduction in pruritus was significantly greater for tacrolimus-treated patients (74% to 89%) than for vehicle-treated patients (51%, P = .027). No serious systemic adverse events were noted, and systemic absorption was minimal. Conclusion: Tacrolimus ointment appears to be safe and effective in children with atopic dermatitis. (J Allergy Clin Immunol 1998;102:637-44.)