Recent studies have demonstrated the important role of CD4+ T cells in the pathophysiology of psoriasis. One of the current hypotheses is that triggering of the psoriatic inflammatory process could be secondary to CD4+ T cell activation by bacterial superantigens in the skin. In this study, IL-2-derived T cell lines were recovered from the blood and the skin of 4 patients with chronic plaque type psoriasis and of 2 patients with allergic contact dermatitis (ACD). Blood and skin T cell lines were tested for their ability to proliferate in vitro to staphylococcal enterotoxin B (SEB) presented by MHC class II expressing antigen-presenting cells. The results showed a significantly higher SEB-induced T cell proliferation in skin T cell lines as compared to blood T cell lines in 3 out of 4 psoriatic patients and in one of the 2 ACD patients. No difference between the skin and blood T cells for their response to phytohemagglutinin was observed. Furthermore the blood T cell lines from both patients and control individuals responded equally well to SEB. Thus psoriatic skin T cell lines were characterized by an enrichment in SEB-responding T cells. Since similar enhancement of SEB-responsive T cells was occasionally found in ACD patients, we propose that SEB could be an environmental factor associated with rather than responsible for psoriatic inflammation.