The in vitro proliferative response of murine bone marrow cells to concanavalin A (Con A) and the effect of anti-Ia serum on the response were studied. The incorporation of [3H]thymidine into cells prepared from the bone marrow of C3H/He, ATL, ATH, and C57BL/6 mice increased in the presence of certain doses of Con A. The bone marrow cells of athymic nude mice were also capable of responding to Con A, but cells prepared from the spleens of such mice were not. The addition of anti-Ia serum to the cultures of bone marrow cells did not affect the responses of these cells to Con A, though their proliferative response to bacterial lipopolysaccharide was greatly reduced in the presence of the serum. Moreover, pretreatment of the bone marrow cells with anti-Ia serum or anti-Thy. 1.2 serum and rabbit complement did not abolish the ability of these cells to respond to Con A. These results indicate that there are some Ia negative and Thy. 1.2 negative cell populations in the marrow capable of responding to Con A. Furthermore, the effect of anti-Ia serum on the Con A-induced proliferative response of the spleen cells which had been obtained from gamma-irradiated and syngeneic bone marrow cell-reconstituted mice was examined. The ability of these cells to respond to Con A increased gradually week by week after the reconstitution. The suppressive effect of anti-Ia serum on the response of these cells gradually became much more pronounced after the reconstitution.