AbstractThese experiments demonstrate that the response of B lymphocytes to particulate antigenin vivocan depend on their stage of differentiation: B lymphocytes differentiating from stem cells were rendered tolerant, while mature B lymphocytes were primed under the same conditions. Lethally irradiated mice of one allotype were repopulated with 13–15 day fetal liver cells from congenic mice bearing another allotype and the effect of antigen on the emergence of responsive B cells determined. B cells, descended from the fetal liver inoculum (identified by their allotype) produced an antibody response to antigen in the presence of additional T cells, 15 days after transfer. Such a response could be prevented by injecting the recipient with alum‐precipitated antigen (but not with deaggregated antigen) shortly after irradiation and reconstitution. This unresponsive state was specific and independent of afferent suppressor mechanisms. Mature B cells, on the other hand, were shown to be primed by alum precipitated antigen in irradiated reconstituted hosts. It was concluded that a fundamental difference exists between the responsiveness of mature and differentiating B lymphocytes. Tolerance in differentiating B lymphocytes is discussed in relation to the acquisition of self‐tole