In mouse skin, tumor development promoted by 'non-genotoxic' carcinogens is closely related to the wound response. In both cases endogenous factors such as cytokines and eicosanoids released primarily from 'activated keratinocytes' play a key role as mediators of inflammation and cellular hyperproliferation. The liberation of interleukin-1 alpha and arachidonic acid from human keratinocytes has been used as an in vitro parameter of irritancy. The results (from experiments with 15 different chemicals) being validated at present in a clinical study indicate a quantitative relationship between irritancy in vivo and mediator release in vitro. In the course of experimental skin carcinogenesis an overproduction of eicosanoids due to a constitutive overexpression of the corresponding enzymes (i.e. PGH synthase-II and 8- and 12-lipoxygenase) is observed. Enzyme inhibitors, for instance nonsteroidal antiinflammatory drugs (NSAIDs), exert a strong tumoristatic effect. Thus, the approach of multistage skin carcinogenesis provides a suitable animal model for a mechanistic evaluation and further improvement of chemopreventive measures such as the inhibition of colorectal tumor development in humans by NSAIDs ('aspirin effect').