In order to develop topical drugs aside from galenic problems, there should be considerations how the skin could be made permeable. For the purpose of receiving an topical basis which favours penetration, ingredients known as auxiliary agents are used, which themselves have an effect on the horny layer and therefore impair the barrier function. The horny layer is irritated to a varying extent due to the chemical and physical properties of such substances. While the concentration of the active ingredients in the epidermis is improved, the irritation of the horny layer must be accepted. When using corticoids this fact may be misconstrued for lacking efficacy. Although auxiliary agents like polyethylene glycol, propylene glycol, o/w emulsifiers, alcohols or acetone show various effects on the horny layer, they all cause dehydration. Experimental data show that for propylene glycol this is clearly concentration related. Other only rarely used solvents like DMSO or dimethyl acetamide have properties directly altering the structure of the horny layer. Even topically applied ingredients only partially show the desired direct or indirect irritative effect on the horny layer. This is true for substances reacting directly with keratin as well as for substances which exhibit cytostatic or cytotoxic effects on the epidermis and for substances that lead to skin irritation. A risk/benefit evaluation is under discussion.