Bacterial colonization on skin or tonsil may influence the clinical response of patients with psoriasis to immunosuppressive drugs. However, few studies have investigated the effects of bacterial superantigens on therapy in these patients. Recently, combination therapy with topical glucocorticoids (GC) and vitamin D3 (VD3) appears to be more effective than GC or VD3 monotherapy for psoriasis. We evaluated the suppressive effects of betamethasone butyrate propionate (BBP), three VD3 derivatives (calcipotriol, maxacalcitol and tacalcitol), cyclosporin and BBP plus VD3, on concanavalin A (ConA)- or streptococcal pyrogenic enterotoxin A (SPEA)-stimulated proliferation of peripheral blood mononuclear cells (PBMC) obtained from 35 psoriasis patients. Drug concentrations effecting 50% inhibition concentration of ConA- or SPEA-stimulated PBMC proliferation were estimated. Cytokine levels of tumor necrosis factor-, -interferon, interleukin-1b, -2, -4, -5, -6, -8 -10 and -12p70 in PBMC culture supernatants were measured with bead-array procedures. Suppression of PBMC proliferation by BBP was significantly lower when PBMC were stimulated by SPEA than when stimulated by ConA. In contrast, the suppressive effects of calcipotriol and tacalcitol increased significantly when PBMC were stimulated by SPEA than when stimulated by ConA. The suppressive effect of BBP on SPEA-stimulated PBMC proliferation was improved significantly by adding 1-1000 ng/mL calcipotriol, compared with BBP alone. Cytokine levels in PBMC culture supernatants were not significantly different between ConA- and SPEA-stimulated PBMC. Calcipotriol and BBP in combination markedly suppressed SPEA-stimulated PBMC proliferation. SPEA produced by colonization of hemolytic streptococci may reduce the efficacy of BBP but not VD3 derivatives in the treatment of psoriasis.