The deficit of humoral immune responsiveness associated with aging was investigated at the level of individual antigen-specific B cells. It was found that mature dinitrophenyl (DNP)-responsive B cells isolated from the spleen of aged mice gave rise to clones of antibody-forming cells that were normal with respect to both the amount and relative affinity of anti-DNP antibody produced. However, although the proportion of immunoglobulin-bearing cells in the spleen of aged mice was normal, the proportion of cells that responded to T cell dependent DNP-specific stimulation (1.1 per 10(6) injected cells) was significantly lower than the proportion that responded when cells were obtained from the spleen of young mice (2.3 per 10(6) injected cells). To examine the origin of this diminution in antigen-responsive B cells, the responsiveness of precursor cells from the B cell generative pool isolated as the surface immunoglobulin negative (sIg-) cells within the bone marrow was evaluated. The frequency of DNP-responsive cells in both intact bone marrow cell suspensions and the sIg- subpopulation was not significantly different when such cells were isolated from aged vs. young individuals. Thus, it would appear that among the immunologic deficits associated with aging is a decrease in the proportion of antigen-responsive B cells, which is associated with maturation of B cell clones in the aged environment and occurs during the migration of cells from the bone marrow to the spleen.