Despite the known specific mediator-related effects of retinoic acid (RA), details of irritant effects of RA on the stratum corneum (SC) remain limited. This study investigates the clinical and functional changes in SC of 6 healthy volunteers induced by 0.05% and 0.1% RA in a 24 h occlusive patch-test as well as in a 10 day open cumulative test-assay compared with 1% sodium lauryl sulfate (SLS). Measurements of transepidermal water loss, stratum corneum hydration, and cutaneous blood flow were performed. SC turnover time (SCTT) was assessed by the dansyl chloride test.In the 24 h patch-test assay, the extent of the SC changes caused by RA, except for scaling, were significantly weaker than those followed by SLS. RA possibly caused a secondary delayed impairment of SC water barrier. In the cumulative test, the skin responses to RA appeared lengthened implying that RA may activate a cascade of proinflammatory mediators which persists even after discontinuing treatment. SLS significantly decreased SCTT more than did RA.RA, like SLS, is capable of inducing certain functional changes in SC possibly mirroring its irritation potential. The SC turnover may be linked with the irritation properties. The distinctive responses to these compounds may provide insight into the different modes of action of RA and SLS.