Both surface Ig (sIg) surface Ia (sIa) have been shown to have important roles in B lymphocyte activation. In order to investigate a possible relationship between these molecules, we studied the effects of cross-linking of sIg on the expression of sIa, as measured by fluorescence-activated cell sorter analysis of lymphoid cells stained with conventional anti-Ia anti-serum or with fluorescein-labeled anti-Ia antibodies. Exposure of cells for 24 hr in vitro to anti-delta, anti-mu, anti-kappa antibodies, or their F(ab')2 fragments induced a very dramatic increase in expression of sIa. Similarly, i.v. injection of anti-delta antibodies into adult mice induced a 2- to 3-fold increase in expression of B cell sIa on spleen, lymph node, and Peyer's patch lymphocytes. There was no increase under these conditions in expression of other B lymphocyte surface antigens, including H-2, 4B9, and 17C9. Furthermore, exposure of B lymphocytes to antibodies directed to B lymphocyte surface antigens other than sIg did not result in an increase in expression of sIa. The anti-Ig-induced increase in sIa expression appeared to be T independent, required cellular protein synthesis, and required more time to occur than did the cross-linking and removal of sIg. This increase in expression of sIa did not occur on B lymphocytes obtained from mice younger than 3 wk old. This increase in expression of sIa may reflect a proximal event in B lymphocyte activation that occurs after cross-linking of sIg by antigen and that may enhance subsequent cellular interactions involving B lymphocytes.