In 18 patients the expression of HLA-A, B, C and -DR antigens on peripheral blood T and B lymphocytes (PBTL and PBBL) was assessed using the lymphocytotoxic microtechnique before and during glucocorticoid administration. During steroid treatment we found a significant reduction in the reactivity of PBBL to allogeneic specific anti HLA-DR antisera as well as a xenogeneic multispecific anti HLA-DR antiserum, corresponding to approx. 1-2 dilution steps. In contrast, the reactivity of both PBBL and PBTL to allogeneic anti HLA-A, B, C antisera and anti beta 2-microglobulin was unaffected during the treatment. Membrane marker studies of the isolated PBBL and PBTL showed no differences in the relative distribution of mononuclear cell subpopulations before and during treatment, which seems to exclude extravascular redistribution of particular HLA-DR positive lymphocyte or monocyte subsets during steroid administration as an explanation for the finding. Incubation of isolated normal PBBL with dexamethasone under various conditions did not affect the reactivity of these cells to anti HLA-DR antisera. Furthermore, preliminary experiments gave no indication of decreased rate of HLA-DR antigen synthesis in the presence of dexamethasone in vitro. Thus, we conclude that glucocorticoid administration in vivo decreases the expression of HLA-DR antigens on PBBL, possibly in an indirect way, the mechanism of which is still unknown.