Although colonization of atopic dermatitis by Staphylococcus aureus is universal and bacterial infection is common, it is not known whether antibiotic therapy is helpful in eczematous children who do not have any signs suggestive of bacterial infection. Fifty children aged 1-16 years with atopic dermatitis took part in a randomized double-blind placebo-controlled study of 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. The change in the mean of the log10 of the counts/cm2 of S. aureus after 4 weeks of treatment was significantly different for patients receiving treatment, compared with the change for those receiving the placebo (P = 0.008). However, the difference in the change at 14 days after stopping treatment was not significant (P = 0.32). Methicillin-resistant strains of S. aureus were cultured from five children during or after treatment. Flucloxacillin did not improve the symptoms or clinical appearance of atopic dermatitis and only temporarily changed skin colonization by S. aureus.