Glucocorticoids are strongly immunosuppressive and are associated with reactivation of some intracellular infections. The plasmacytoid dendritic cell is a rare blood mononuclear cell detected through its production of IFN-alpha in response to herpes simplex virus and by surface immunophenotyping. We here report that steroid administration results in a decrease of IFN-alpha generation of approximately 25-fold, accompanied by reduction in circulating plasmacytoid dendritic cell numbers. Both parameters return to normal within days after steroid cessation.