Cell death is a prominent feature of B cell development. For example, a large population of B cells dies at the pre‐B cell stage presumably due to the failure to express a functional immunoglobulin receptor. In addition, developing B cells expressing antigen receptors for self are selectively eliminated at the immature B cell stage. The molecular signals that control B cell survival are largely unknown. The product of the bcl‐2 proto‐oncogene may be involved as its overexpression inhibits apoptotic cell death in a variety of biological systems. However, the physiological role of the endogenous Bcl‐2 protein during B cell development is undetermined. Here we show a striking developmental regulation of the Bcl‐2 protein in B lymphocytes. Bcl‐2 is highly expressed in CD43+ B cell precursors (pro‐B cells) and mature B cells but downregulated at the pre‐B and immature B cell stages of development. We found that Bcl‐2 expressed by B cells is a long‐lived protein with a half‐life of approximately 10 h. Importantly, susceptibility to apoptosis mediated by the glucocorticoid hormone dexamethasone is stage‐dependent in developing B cells and correlates with the levels of Bcl‐2 protein. Furthermore, expression of a bcl‐2 transgene rescued pre‐B and immature B cells from dexamethasone‐induced cell death, indicating that Bcl‐2 can inhibit the apoptotic cell death of progenitors and early B cells. Taken together, these findings argue that Bcl‐2 is a physiological signal controlling cell death during B cell development.