The propensity of chemicals and of preparations/formulations to give rise to skin irritation is an important toxic endpoint which needs to be properly assessed in order that irritant contact dermatitis in man can be minimized. For over half a century, the rabbit has been the primary species providing an in vivo measure of skin irritancy, usually via the Draize test. This has been supplemented from time to time by testing of some types of finished products in human volunteers to confirm their lack of significant irritation potential. However, for various reasons, the rabbit is not necessarily an accurate predictor of skin irritation potential and there is considerable demand for elimination of its use on animal welfare grounds. If this is the case, then what are the alternatives? Some effort has been directed to the development of in vitro assays using cytotoxicity endpoints as a surrogate for irritancy. Most recently developed have been three dimensional skin models where substances can be applied directly to a stratum corneum-like surface. In parallel, there has been also the development of more sophisticated endpoints such as cytokine release. However, validation of these approaches will prove difficult in the absence of a skin irritation dataset produced using a standardized method against which to judge their performance. Since it would be inappropriate to use animals for this purpose, this leads to a consideration of another alternative, which is really not 'an alternative', that is to use man. With careful protocol design, the skin irritation potential of substances can be assessed using human volunteers. Furthermore, there are then many existing protocols which permit risk assessment studies to be carried out on human volunteers. Consequently, before we expend our efforts trying further to develop and validate in vitro models, it may be well worthwhile developing a quality human skin irritation dataset against which to validate them by undertaking ethical and practical studies which use the endpoint of concern (skin irritation) in the species of concern (man).