B cells from CBA/N mice did not form colonies in semisolid agar cultures under circumstances where normal B-cell clonal proliferation is linear with respect to the number of functional cells cultured. This was no due to the unresponsiveness of CBA/N cells to mitogens, and under appropriate liquid culture conditions many CBA/N lymphocytes differentiated to plasma cells containing large amounts of IgM in response to LPS. On the other hand, the same cells proliferated and matured poorly in liquid cultures prepared at low-cell density. The frequency of granulocyte-macrophage progenitors and multipotential hemopoietic stem cells in bone marrow, ability of peritoneal macrophages to elaborate soluble enhancing factors, and levels of serum inhibitors were normal in CBA/N mice. Together with the results of cell-mixing experiments, these findings confirm the selective and intrinsic nature of the CBA/N deficiency. It is suggested that the B-cell cloning technique may be of value in selectively enumerating and assessing functional capability of thymus-independent B cells. C3H/HeJ mice which have previously only been known to be hyporesponsive to certain forms of lipopolysaccharide had a subnormal incidence of colony-forming B cells.