The percutaneous absorption of selected radiolabelled compounds through female rat skin was determined after their application in a petrolatum vehicle. Absorption was measured during a 5-day period by in vivo and in vitro techniques. Benzoic acid, acetylsalicylic acid, urea, and caffeine were selected because of their differing skin permeability rates. Absorption was measured in vivo from urinary excretion data and in vitro with excised skin in diffusion cells. When skin absorption was expressed as the percentage of applied dose, the values obtained in vitro with urea was 7.2%. Since similar values were obtained in vivo, permeability measurements of these compounds with excised skin appear reliable. With the in vitro data, the rate of skin absorption was more accurately stated in the form of a permeability constant.