The ability of the skin of man, cat, rabbit, and rat to hydrolyze or otherwise metabolize paraoxon (E 600, or diethyl 4-nitrophenyl phosphate) or parathion (E 605, or diethyl 4-nitrophenyl thiononophospate) was investigated using the Warburg technique and paper chromatography. Parathion was not hydrolyzed or transformed into paraoxon by the skin of any of the species tested. Paraoxon, on the other hand, was hydrolyzed by skin from man, cat, and rabbit. This reaction, which was enzyme in nature, occurred at the fastest rate in the rabbit. In this tissue, about 20 percent of the paraoxon was hydrolyzed in 1 hour by 1 gram of skin at 25C, while only about one percent was converted by skin from man or cat. The relation of these findings to the percutaneous absorption of these compounds was discussed.