Inflammatory skin T cells were cloned in an antigen-independent way from lesions of patients with experimentally induced nickel-contact dermatitis. In three experiments 7-15% of the CD4+8- T lymphocyte clones (TLC) appeared to be specific for nickel in a proliferation assay. These proliferative response of nickel-specific TLC required the presence of antigen-presenting cells (APC) and were restricted by HLA class II molecules. All TLC recognized nickel presented by APC from epidermal skin. Remarkably, 5 out of 8 nickel-specific TLC exclusively recognized nickel when presented by these skin-specific APC whereas 3 out of these 8 clones could also recognize nickel presented by APC from peripheral blood. The critical APC within the fractions of epidermal cells and peripheral blood appeared to belong to the family of dendritic cells, i.e. Langerhans cells and circulating dendritic cells, respectively.