Purified human C3b added to mouse lymphocyte suspensions triggers stimulation of up to 50% of the B lymphocytes; the stimulation was detected by increased incorporation of thymidine, blast cell formation, and antibody secretion (K.-U. Hartmann and V. A. Bokisch, J. Exp. Med. 142, 600, 1975). Purified human C3 does not stimulate these lymphocytes. Addition of purified C3b inactivator (C3bINA) (M. K. Pangburn, R. D. Schreiber and H. J. Müller-Eberhard, J. Exp. Med. 146, 257, 1977) — 1 to 2 µg C3bINA to 100 µl lymphocyte cultures — strongly inhibited the stimulation of B lymphocytes induced in the presence of C3b or LPS. This inhibition was not dependent or enhanced by the addition of purified human β1H-globulin. The inhibition caused by the addition of C3b INA was reduced or prevented by the presence of FCS. Preincubation of C3b with C3bINA did not inactivate the activity, leading to stimulation in the presence of FCS. These experiments suggest an activity of C3bINA directed toward the cells involved.