GERMINAL centres are dynamic microenvironments of B-lymphocyte differentiation, which develop in secondary lymphoid tissues during immune responses(1-3). Within germinal centres, activated B lymphocytes proliferate and point mutations are rapidly introduced into the genes encoding their immunoglobulin receptor(4-10). As a result, new specificities of B cells are created, including those with a heightened capacity to bind the immunizing antigen(4-11). Immunoglobulin gene mutation can also lead to reactivity to self antigens(12-14). It has been suggested that any newly formed self-reactive B cells are eliminated within the germinal centre in order to avoid autoimmunity(15,16). Here we present evidence that antigen-specific, high-affinity, germinal-centre B cells are rapidly killed by apoptosis in sits when they encounter soluble antigen. The effect seems to act directly on the B cells, rather than through helper T cells. Furthermore, the apoptosis is unique to germinal-centre cells, and is only incompletely impeded by constitutive expression of the proto-oncogene bcl-2. This phenomenon may reflect clonal deletion of self-reactive B cells within germinal centres.