A double-blind, randomized trial was conducted to determine the influence of topical steroid therapy on atopic skin flora. The bacteriological and clinical effects of desonide (Locapred®), compared with those of its excipient, were studied in 40 children. Clinical scoring and bacteriological sampling were performed before the start of the trial and after 7 days of once-daily topical treatment. Before treatment, no differences in clinical score or Staphylococcus aureus colonization were noted between the two groups. After treatment, the clinical score improved (P<0.001) in the desonide group, and S. aureus density decreased dramatically (P<0.001). In the excipient group, no significant differences in clinical score or S. aureus density were noted. A comparison of the two groups demonstrated statistically significant differences with regard to clinical score (P<0.001) and S. aureus density (P<0.05). These results show the efficacy of topical corticosteroid treatment alone on S. aureus colonization in atopic skin, and confirm the critical role of inflammation in bacterial colonization.