In young NZB x NZW (B/W) F1 mice there was a population of B cells that were hyperresponsive to interleukin 2 (IL-2) and that proliferated but did not differentiate, even in the absence of a prior activation signal, and hence were already stimulated in vivo and were prepared to respond to IL-2. These B cells belonged to the population that was nonadherent to the Sephadex G-10 (G-10) column. We found that such hyperresponsiveness was progressively reduced with the aging of these mice. This event did not appear to be related to the age-associated changes of IL-2 receptors on B cells, since the IL-2-binding ability and the density of IL-2 receptor alpha expressed on B cells in culture did not differ between the young and the old mice. Studies suggested that two major mechanisms are responsible for the age-associated decline in the IL-2 responsiveness of B cells. First, the capacity of IL-2 hyperresponsiveness of such B cells decreases in B/W F1 mice with aging, probably through further activation and differentiation of the B cells. Second, the G-10 adherent, but not nonadherent, B cells from the aged mice inhibit the IL-2 response of G-10 nonadherent B cells. The G-10 adherent B cells from the old mice also inhibited the IL-2 production of T cells from the young B/W F1 mice. Taken together, it appears that young B/W F1 mice bear a population of B cells already stimulated so that they can respond to IL-2 without prior stimuli. With aging, activation of the B cells progresses and they appear to down-regulate the IL-2 hyperresponse of B cells and the IL-2 synthesis by T cells.