A three-dimensional reconstruction of living skin - the skin equivalent - has been modified to accept materials that can be applied topically to the skin. Using an irritant gel containing 10% benzoyl peroxide, changes in the skin equivalent model were investigated. Histologically, epidermal necrosis and vacuolar change were observed within 4-6 hr after topical application. Using skin equivalents prelabelled with [3H]arachidonic acid, studies involving direct measurement using HPLC and radioimmunoassay have indicated the release of potent lipoxygenase products, such as leukotriene B4 and 15-hydroxyeicosatetraenoic acid. These preliminary results suggest that the skin equivalent may prove to be a useful in vitro model for the prediction of cutaneous toxicity of topically applied substances.