The effect of protracted aqueous contact of rat skin on its permeability to methanol, n-butanol, and n-hexanol was investigated. With the aid of small diffusion cells, sets of intermittent permeation experiments, each approximately 7 hr in duration, were performed on excised rat skin sections over periods lasting several days, and permeability coefficients were calculated as a function of the duration of the hydration. The permeability coefficient of methanol increased gradually to an asymptote 2.5 times higher than the initial value over the first 80 hr of immersion and then remained essentially invariant through an additional 70 hr. In contrast, the butanol permeability coefficient increased by only a small fraction (approximately 25%) through the first 5 hr of hydration, and it remained at the higher value through to the end of the experiment at 80 hr. For more hydrophobic hexanol, the permeability coefficient increased by approximately 40% over the first 10 hr and then declined, returning to near the initial value by the second day. It was relatively constant past this point--up to 150 hr. When these data were compared with similarly obtained data from earlier studies involving two strains of mice, the Swiss mouse and a hairless mouse mutant, parallelism was noted in the behavior of the rat and Swiss mouse skins, which set them both apart from the behavior of the skin of the hairless mouse. The comparison suggests that, irrespective of animal species, the development of a thick coat of hair occurs with commensurate functional changes in the chemical barrier properties of the epidermis.