The number of common lymphoid progenitors (CLP) and their pre-pro-B and pro-B cell progeny is reduced in old mice, but the age-related changes responsible for these declines have not been fully elucidated. The aim of this study was to provide additional insights into the impact of senescence on early B cell development by analyzing the CLP and pro-B cell compartments under steady-state conditions and after cytoablation with 5-fluorouracil. 5-Fluorouracil subjects the hemopoietic system to acute stress and has the advantage of revealing defects in progenitors that may otherwise be subtle. The data demonstrate significant, age-related defects in the proliferative potential of early B cell precursors and suggest that the ability of CLP to differentiate into pre-pro-B cells is also compromised by senescence. These age-related changes in early B lymphopoiesis do not result from a general defect in HSC or the bone marrow microenvironment that impairs development in all hemopoietic lineages. Instead, data demonstrating that myeloid progenitor number and developmental potential do not decline with age indicate that B lymphopoiesis is particularly sensitive to defects that accumulate during senescence.