Conventional glucose-containing peritoneal dialysis solutions (PDS) with a high glucose degradation product content accelerate leukocyte apoptosis and impair peritoneal defense. Mononuclear cells are less sensitive than neutrophils to PDS-induced apoptosis, suggesting that they may express antiapoptotic molecules. Since apoptosis induced by PDS requires Bax, we explored the role of an antiapoptotic protein of the same family, Bcl-xL, in PDS-induced apoptosis in cultured peripheral blood mononuclear cells and monocytic THP-1 cells. In these cells, conventional PDS decreased the expression of Bcl-xL protein with a temporal pattern compatible with their lethal effect. Inhibition of Bcl-xL also induced mononuclear cell apoptosis. A cell-permeable TAT-BH4 peptide that contains the BH4 domain of Bcl-xL prevented mononuclear cell apoptosis induced by PDS. These data suggest that Bcl-xL protects mononuclear cells from apoptosis induced by bioincompatible PDS and that Bcl-xL-like molecules should be explored to prolong leukocyte survival and potentiate peritoneal defense during peritonitis.