Detergents are involved in the causation of contact dermatitis and in promoting percutaneous absorption of toxic chemicals, but limited information is available to allow an assessment of their relative effects on the skin barrier function. The effect of detergents on skin permeability to water and nickel was examined in an in-vitro model using human skin. Twenty-four of the most widely used detergents were studied. After a two-hour exposure to an aqueous detergent solution, penetration of labeled model compounds was followed for 66 hours. Interindividual variation was substantial, but 12 of the detergents caused statistically significant increases in the penetration of water, nickel, or both. Nonionic detergents were as likely as anionic detergents to have this effect. This study demonstrates that useful information may be obtained by a simple in-vitro method, and that such data may provide a basis for substitution efforts.