In 3 separate experiments mice were exposed to various concentrations of fossil liquids obtained from coal, oil shale or natural petroleum. All materials were capable of inducing squamous cell carcinoma, but potency differed substantially. Skin carcinogenicity was markedly greater for coal or oil shale liquids than for natural petroleums. None of the syncrudes approached the skin carcinogenicity of a pure reference carcinogen, benzo(a)pyrene (BP). It is unlikely that determination of the concentration of an active compound in material applied to the test animal will allow meaningful comparison among the diverse agents of interest to the synthetic fuels industry. To better establish the relationship between actual tissue dose and surface concentration various in vitro and biochemical measures of hydrocarbon-skin interaction were investigated to determine which, if any, could serve as a more definitive measure of surface dose. Results, using BP as a marker carcinogenic hydocarbon, suggest that carcinogenic crudes inhibit BP metabolism in skin organ culture and the interaction of BP adducts with epidermal DNA, in vivo.