CD5 is a pan-T cell antigen which is expressed on a minor subset of normal B lymphocytes and on most chronic lymphocytic leukemia B cells (B-CLL). In this study, it is demonstrated that interleukin (IL) 4 down-regulates the surface expression of CD5 on tonsil B cells and B-CLL cells, but not on T cells. IL 4 inhibits both the spontaneous and the phorbol myristate acetate (PMA)-induced hyperexpression of CD5 on tonsil B cells. In contrast, IL 4 only suppresses the PMA-induced hyperexpression of CD5 on B-CLL, whereas the spontaneous CD5 expression is essentially unaffected. The IL 4 concentrations required to down-regulate CD5 are the same as those required to up-regulate CD23. The IL 4-mediated down-regulation of CD5 is an intrinsic property of this IL, since an anti-IL 4-neutralizing antiserum blocks this effect. Interferon (IFN)-gamma, which inhibits the IL 4 induced CD23 expression, does not block the IL 4-induced down-regulation of CD5. Recombinant IL 1 alpha, IL 2, IL 3, IL 5, IL 6, tumor necrosis factor (TNF)-alpha, IFN-gamma and granulocyte macrophage colony-stimulating factor neither inhibit nor stimulate CD5 expression on B cells, therefore suggesting that the capacity to down-regulate CD5 expression on B cells is specific to IL 4.