We observed hydrocortisone and benzoic acid absorption in relation to experimentally induced in vivo damaged skin models in the hairless guinea pig. Radioactivity of the drugs in urine was calculated as absorbed dose. Both drugs have different patterns of excretion in urine. D amaging the skin abolished some barrier function and increased the absorption of both model drugs. With cellophane-tape-stripped skin, the absorption was increased 3 times and 2 times for each drug, respectively. Irritation with 2% sodium lauryl sulfate increased absorption by a ratio of 2–4 times. Defatting with chloroform/methanol (2:1) mixture increased absorption to the greatest extent (5- and 2.7-fold). The possible mechanism of a delipidization effect was considered in view of a visible skin lesion and inflammatory reaction. Precautions are proposed for those with damaged/diseased skin in dealing with topical medications or handling solvents.