The permeability of human epidermis to many phenolic compounds can be related to octanol/water partition coefficients. For a series of compounds having similar diffusion coefficients and showing an increase in lipophilic character, the maximum flux will be obtained with the less lipophilic compounds because the solubility decreases more rapidly than the partition coefficient increases. The penetration of some phenolic compounds is concentration dependent, a constant permeability coefficient being observed below a threshhold concentration above which the permeability coefficient increases with concentration. The increase in the permeability coefficient is attributed to ‘damage’ to the epidermis and a reduction in its diffusional resistance. A relation between the ability of a substance to damage the skin and the lipophilic character (or more generally the penetration flux) of the substance was found. A number of substances do not appear to ‘damage’ the skin due to insufficient substance partitioning or penetrating into the stratum corneum. This ‘cut-off’ in effect is generally observed for the more lipophilic substances. For a series of compounds, maximum damage will be obtained with the less lipophilic compounds in accordance with the predicted concentrations of the substance in the stratum corneum. Phenolic compounds appear to interact with the skin by protein denaturation although for the more lipophilic compounds some degree of ‘plasticization’ of the lipids is evident.