Background Streptococcal infection is strongly associated with guttate psoriasis (GP) and may also exacerbate chronic plaque psoriasis (CPP), possibly through the release of superantigenic toxins. Objectives To investigate superantigen-induced generation of cutaneous lymphocyte associated antigen (CLA) -positive lymphocytes in GP compared with CPR Objectives To investigate superantigen-induced generation of cutaneous lymphocyte associated antigen (CLA) -positive lymphocytes in GP compared with CPR Methods Peripheral blood lymphocyte (PBL) expression of CLA and T-cell receptor VP chain was assessed in patients with CPP and with active and resolved GP. Expression of superantigen-reactive VP families was compared with in vitro superantigen-induced peripheral blood mononuclear cell (PBMC) proliferation. Results Peripheral blood mononuclear cells from patients with active GP showed a twofold increased proliferation after stimulation with streptococcal pyogenic toxins A and streptococcal pyogenic toxins C compared with controls (P < 0.01), whereas the response to the staphylococcal toxins and mitogenic stimulation was the same in all groups. Peripheral blood lymphocytes (PBL) from patients with active GP showed increased use of the superantigen-reactive families V beta2 (P < 0.01) and V<beta>17 (P < 0.05), which was not evident in the other patient groups or controls. This pattern of VP expression was only observed in CLA-positive T cells. Furthermore, there was a positive correlation between V<beta>2 expression and enhanced proliferation after stimulation with SPEA (r = 0.82, P < 0.01) and SPEC (r = 0.74, P < 0.05) in active GP. Conclusions This study supports the concept that streptococcal infection precipitates acute GP at least in part through superantigen driven generation of Vp-restricted CLA-positive skin homing lymphocytes, whereas we could find no evidence for a similar mechanism occurring in the maintenance of stable CPP.