Since it is of high importance to establish the skin irritation potential of industrial chemicals, toxicologists developed tests on various skin models. Most test data come from the rabbit Draize test, but its reproducibility is questionable. Some human in vivo test data exist, but they concern only few compounds. The emergence of new tools such as reconstituted human skin tissues offers a promising future to alternative methods. We describe here two in vitro skin irritation test protocols performed on reconstituted human epidermis. One is a direct topical application test and the other an in vitro patch test. Both protocols were performed using multiple endpoint analysis including cell viability (MTT reduction), histology, and IL-1alpha release. Fifty chemicals were tested: 20 compounds were used in the ECVAM pre-validation study and 30 products were previously tested in a human in vivo patch test. These in vitro skin irritation tests have not only the advantages of enhanced convenience and of reduced costs, but a good reproducibility is observed by endpoint, and by compound. A prediction model is proposed to classify the chemicals as irritant or non-irritant, and the results are compared to available rabbit and human data. We do not wish to overgeneralize from these 50 compounds; but, instead suggest that this data set be extensively extended to include chemicals of varying physico-chemical properties.