Since the original demonstration by Amsbaugh et al. (1) that a sub-line of CBA/H (CBA/N) mice has a recessive X-linked genetic defect which prevents them from responding to type III pneumococcal polysaccharide this sub-line of mice has come under intensive study, particularly by Scher and his colleagues (2–9). These workers have established that the X-linked defect is expressed in B cells (4) and that by a number of criteria the T cells of the mice with the defect are indistinguishable from those of appropriate control mice (4). They have further shown that the defect preferentially inhibits the response to so called “thymus-independent antigens” (1, 2, 5, 9); it leads to a much smaller deficit in the response to “thymus-dependent antigens”. CBA/N B cells are intrinsically defective and are not influenced by the environment in which they reside (4, 9). The defect can best be explained as a failure of maturation or differentiation in that it has been shown that adult CBA/N mice lack a population of B cells which is also lacking in young (but not mature) normal mice (6, 7).