Local activation of T lymphocytes appears to play an important role in psoriasis and autoimmune skin disease. 1 alpha,25-dihydroxyvitamin D3 and the vitamin D3 analog calcipotriol have been shown to inhibit immune induction in vitro. The purpose of the present study was to investigate the in vivo effect of calcipotriol on Langerhans cells in normal human skin and to determine the effect of 1,25-dihydroxyvitamin D3 and calcipotriol on isolated Langerhans cells to induce autologous T-cell proliferation. Using confocal laser scanning microscopy of epidermal suction blister roofs, it was found that application of calcipotriol cream to normal human skin for 4 d resulted in a dose-dependent decrease in the number of CD1a+ cells with a dendritic morphology and in the number of dendrites per cell. The suppressive effect of calcipotriol on Langerhans cells was as strong as that of the potent corticosteroid mometasonfuroate. In Langerhans cell-enriched cell suspensions (60-97% pure) isolated from normal human skin, 1,25-dihydroxyvitamin D3 and calcipotriol (10(-8)-10(-7) M) significantly suppressed their ability to stimulate antigen-dependent T-cell proliferation. Furthermore, the vitamin D receptor was detected by Western blot analysis in the isolated Langerhans cells. Neither immunohistochemical studies nor flow cytometry of Langerhans cells showed any change in the human leukocyte antigen-DR expression after 48 h culture with antigen with or without calcipotriol. It is proposed that the inhibitory effects of the vitamin D3 on Langerhans cells may induce immunosuppression in the skin.