The effect of age on the mitogenic and antigenic responsiveness of B cells is examined in spleen cell cultures of CBA/N and (CBA/N X DBA/2) F1 mice. Spleen cells from young male F1 mice (4- to 6-wk old) show lower mitogenic responses to lipopolysaccharide, a lower frequency of sheep erythrocytes (SRBC)-reactive B-cell precursors, and a lower percentage of Ig-bearing cells than age-matched female F1 mice. The expression of all three functions were found to increase with the age of the F1 male mice. Whereas male F1 mice at 60 wk of age showed an equivalent percentage of Ig-bearing spleen cells and a similar mitogenic responsiveness to LPS when compared to adult female F1 mice, the frequency of SRBC-reactive B-cell precursors remained threefold lower. These findings reveal that there is a slower maturation of B cells in mice expressing the X-linked defect and suggests that the defect has differential effects on the mechanisms of antigen and mitogen activation of B cells.