Investigations of in vitro procedures to predict the potential of substances as skin irritants and as allergens inducing delayed hypersensitivity (contact dermatitis) are described, with indications of possible advances and known limitations. The examination of keratome slices of skin for release of enzymes, for changed histochemistry and for utilization of radioisotope-labelled amino acids will detect weak irritants but is of doubtful value for moderate irritants and will detect corrosive substances only through their inhibition of all cell activities. Fibroblast cultures, tested with Clostridium perfringens toxin and chemicals, show similar limitations in detecting moderate or severe irritants. Fibroblast cultures can be made more relevant to epidermal exposure by an overlying layer of agar containing keratin. In vitro tests to detect induction of sensitizing potential for delayed hypersensitivity have made little progress. The most promising approach is to treat antigen-presenting Langerhans cells with antigen and co-culture with lymphocytes. The lymphocytes may be examined for changes in receptor expression, for synthesis of interleukin 2, and possibly for responses to allergen if sufficient cells become specifically sensitized. There are several in vitro techniques to detect responses of in vivo- or in vitro-sensitized lymphocytes treated with antigen.