Cellular CD23 has been implicated in various biologic and pathologic processes. Here, we have studied the regulation of B cell CD23 expression and function by the synthetic corticosteroid, dexamethasone (DEX). We report that DEX acts directly on B lymphocytes to down-regulate IL-4-induced CD23 expression, whereas in parallel the IL-4R is up-regulated. Down-regulation of CD23 occurred at the cell surface and for shed material in culture medium. EBV infection of B cells is linked to development of lymphoproliferative diseases, including lymphoma, and there is evidence that EBV-stimulated CD23 expression may be instrumental in the inappropriate survival of infected cells. We have determined that treatment of EBV-infected cells with IL-4 leads to a synergistic up-regulation of B cell CD23. Furthermore, infection of B cells by EBV introduced a relative resistance to the down-regulatory effects of DEX on IL-4-induced CD23 expression.