CD40L, a membrane protein of activated T cells, interacts with the B cell receptor CD40. This interaction has been implicated in the rescue of germinal center B cells from apoptosis and in the rescue of WEHI-231 B lymphoma cells from sIg-induced apoptosis. In this report, we have demonstrated that the signal mediated by CD40L acts upon bcl-x, a bcl-2 homologue. bcl-x expression is strongly enhanced by CD40 receptor engagement, while there is little or no induction by sIg cross-linking. The expression of bax and bcl-2 is not significantly affected by either CD40L or sIg cross-linking. Antisense but not sense phosphorothioate oligonucleotide for bcl-x can partially block this CD40-mediated apoptotic rescue. This result suggests that the up-regulation of bcl-x by CD40L plays an important role in CD40-mediated apoptotic rescue in murine B cells.