Psoriasis is a T cell-mediated inflammatory skin disease that has been associated with infections by group A beta-haemolytic streptococci. In a previous study of patients with active psoriasis we demonstrated an increased frequency of circulating Th1-like cells that responded to 20 amino acid (aa) streptococcal M-peptides sharing sequences with human keratin. These cells disappeared after ultraviolet B (UVB)-induced clinical remission. Using T cells from the blood of 17 psoriatic patients and 17 healthy controls we have now compared the numbers of interferon-gamma (IFN-gamma)-producing cells induced by seven 18-20 aa keratin peptides and five corresponding M-peptides. The most frequent and strongest responses were observed to a peptide from keratin 17 that shares ALEEAN sequence with M-protein. The responses to this peptide were stronger than to the corresponding M-peptide containing the ALEEAN sequence. After UVB treatment T cell responses to all the M- and keratin peptides were abolished, while responses to the positive control antigen streptokinase/streptodornase (SK/SD) were not affected. These findings are consistent with the notion that aa sequences which keratin has in common with M-protein may be a major target for autoreactive T cells in psoriasis.