Methylprednisolone aceponate (MPA, Advantan*) is a new corticosteroid diester developed for the topical treatment of steroid-responsive skin diseases. It is readily hydrolyzed in the skin resulting in its activation, and on absorption into the blood, the metabolites are rapidly inactivated by conjugation with glucuronic acid thus minimizing systemic corticoid effects. 276 patients suffering from atopic dermatitis with symmetrically distributed lesions were enrolled in three double-blind controlled right/left half-side trials comparing: (1) 0.1% MPA twice daily with MPA once daily (n= 88); (2) 0.1% betamethasone valerate (BMV) twice daily (n= 94); and (3) 0.1% MPA once daily with 0.1% BMV twice daily (n= 94). There were no differences between MPA used once and twice daily, respectively, with 66% complete healing and 27% marked inprovement (overall response rate 93%) as compared with BMV twice daily with 68% complete healing and 30% marked improvement (response rate 98%). The local and systemic tolerance was excellent.