Exposure to UV radiation has been shown to induce cutaneous biological changes and chemical modifications of exogenous compounds. The application of sunscreen limits UV-induced cutaneous injury. Besides damages can also be elicited by some chemicals following UV irradiation (phototoxic agents). The effects of UVA and UVB irradiation have been studied in vitro on a reconstituted epidermis (EPISKIN) for cytotoxicity (MTT conversion test) and release of a proinflammatory mediator, interleukin 1alpha. When compared with irradiated human keratinocyte monolayers, the results obtained with EPISKIN showed the protective function of the stratum corneum to UVB. Topical application of a UVB sunscreen directly on EPISKIN stratum corneum showed a concentration-dependent relationship between the active ingredients and UVB-induced damages evaluated by both parameters. When chlorpromazine was tested on EPISKIN, an increase in cytotoxicity and release of interleukin 1alpha followed UVA irradiation. A non-cytotoxic dose of 10 J/cm2 of UVA induced a 20-fold decrease in the chlorpromazine IC50. The chlorpromazine-induced inflammatory reaction was also reflected by a more intense release of interleukin 1alpha in the underlying media of EPISKIN. Thus this proinflammatory mediator seems to be relevant as a phototoxic marker. The EPISKIN model may be a useful tool in the study of UV-induced cutaneous damage. The design of this study represents an advance in non-animal test development and could be of great interest in the determination of phototoxic or photoprotective effects of compounds in vitro.