Hairless mice, effective as a model for the prevention of steroid atrophy by tretinoin, were used to examine the effectiveness of tretinoin as a therapeutic agent for the reversal of steroid atrophy. Skh-1 mice were treated topicaUy with 0.05% clobetasol propionate for 3 weeks, followed by either 0.05% tretinoin or vehicle for 3 weeks. Appropriate controls were included. Striking tretinoin effects were a marked reversal of epidermal and subcutaneous muscle atrophy and an increase in the steroid-reduced glycosaminoglycan levels that significantly exceeded vehicle effects. Rapid recovery of fibronectin, collagen and non-collagenous protein levels with vehicle treatment confounded tretinoin results. Although the hairless mouse is not an ideal model for the treatment of steroid atrophy, the results suggest a possible therapeutic value for tretinoin.