Long-term application up to 8 weeks of a 10% urea solution provokes an epidermal thinning expressed in a decreased number of DNA-synthetizing cells. This epidermal reaction cannot be established after topical use of HTH® emulsion. Even by daily application during 8 weeks no change was seen. The absence of epidermal thinning after HTH exposure can be explained as an additive effect of urea and the other constituents of the HTH emulsion. This opinion is supported by the results after application of urea together with Tween 60 in that the acanthogenic effect of Tween 60 is decreased by addition of urea. On the other side, the therapeutic efficiency of 10% 5-fluorouracil solution can be increased remarkably by preliminary treatment with HTH emulsion. These findings could reach importance in the topical therapy with regard to the possibility to improve the effectiveness of any drug by addition of, or preliminary treatment with, urea