Since their first description in 1850, hairless mice have been widely used in scientific research. One major aspect of their use is skin pharmacology in general and skin penetration studies in particular. The term ‘hairless mouse’ does not distinguish a unique animal: it is a collective, descriptive name for a large group of different strains of various genetic origin. It is therefore important to precisely define the strain of mice used in a study. The available information on comparative penetration studies in man and in hairless mouse is sometimes contradictory. Some compounds will penetrate in an almost similar manner, whereas others differ in at least one logarithmic order, the human skin being the less permeable. Skin permeability is influenced, among others, by the physicochemical qualities of the compound under investigation. To obtain a clearer view on the suitability of the hairless mouse model in skin penetration studies, it should be useful to study this issue prospectively in a systematic fashion.