C57BL/10ScCr mice are low responders to the alpha 1-6 epitope of dextran B512, although other C57BL mice are high responders. Both thymus-independent and thymus-dependent forms of dextran failed to induce an immune response in C57BL/10ScCr mice, but dextran functioned as a good carrier for antihapten responses in this strain. Dextran is a potent polyclonal B cell activator for cells from C57BL/10ScCr mice, although such cells are not activated by LPS. The C57BL/10ScCr mice possess the Igh-V gene coding for antibodies against dextran and the antidextran antibodies induced in (A X C57BL/10ScCr)F1 hybrids share an idiotype with antidextran antibodies produced in C57BL/10 mice. Bone marrow cells from C57BL/10ScCr mice do not respond to dextran when transferred into lethally irradiated C57BL/10 mice and C57BL/10 cells transferred into C57BL/10ScCr mice give a strong antidextran response. Thus, B cells having both the Igh-V gene coding for antibodies against dextran and activation receptors for dextran cannot be activated into antibody synthesis against any form of this immunogen. This determinant specific immunodeficiency suggests the existence of as yet unknown regulatory influences on Igh-V gene expression or B cell activation.