Background: Fluticasone propionate is a novel and potent corticosteroid. It seems to have an improved therapeutic index on the basis of studies on skin thinning and suppression of hypothalamic-pituitary-adrenal axis. Objective: We assessed the efficacy and safety of fluticasone propionate (FP) 0.05% cream once daily as compared with clobetasone butyrate (CB) 0.05% cream twice daily in children with atopic dermatitis (AD). Methods: Twenty-two children (3 to 8 years old) with moderately active AD received either FP once daily or CB twice daily. Severity of AD was scored weekly by means of the modified Scoring of Atopic Dermatitis system (SCORAD) and treatment was either stopped when skin lesions were almost cleared (SCORAD < 9) or after 4 weeks. Cortisol excretion was determined by means of 24-hour urine before and after treatment. Results: Twenty-one children completed the study. After 1 week of treatment, mean SCORAD significantly decreased in both treatment groups. After 2, 3, and 4 weeks cumulatively, 8, 12, and 16 children, respectively, were clinically healed (SCORAD < 9). No significant differences in efficacy were observed between the two treatments. Urinary cortisol excretion was not altered by either of the treatments. Two weeks after discontinuation of active treatment, mean SCORAD had increased to 22, but still was significantly lower than that at the beginning of the study. Conclusion: Once-daily treatment with FP is as safe and effective as twice-daily treatment with CB in children with AD. All children experienced an exacerbation of AD within 2 weeks after treatment was withdrawn, indicating the need for long-term “intermittent” treatment. (J Am Acad Dermatol 1998;39:226-31.)