By the use of a rosette method allowing the detection at the cellular level of lymphocytes simultaneously binding Fc- and C'3-sensitized red cells it was found that about 70% of the rosette-forming cells from spleens of nude and normal mice possessed receptors for both Fc and C'3, whereas 30% only had Fc receptors. Very few, if any, lymphocytes possessed only C'3 receptors. The B-cell mitogens, purified-protein derivative of tuberculin (PPD), lipopolysaccharide from Escherichia coli (LPS), and pneumococcal polysaccharide type SIII (SIII), induced marked changes of these receptor-bearing lymphocytes. PPD caused a rapid loss of cells capable of binding C'3 and a concomitant increase of only Fc-binding cells, which was detected after only 24 h. LPS and SIII induced analogous changes, but they were not detected until 48 h and were not complete until after 72 h. It is suggested that immature lymphocytes possess both Fc and C'3 receptors and lose the latter receptor upon differentiation induced by B-cell mitogens PPD. and LPS would affect different populations of B cells, PPD-activating cells that have already reached a higher differentiation stage, whereas LPS and SIII would activate more immature B cells.