Specific anti-Ia serum in combination with rabbit complement removed the B lymphocyte population normally responsive to LPS mitogenic stimulation. Significant inhibition of this proliferative response was also obtained by brief periods of cell pretreatment with anti-Ia antibodies, but not with specific anti-H-2K antibodies. The population of splenic B cells resistant to anti-Thy-1.2 serum and complement was blocked in a very similar manner by anti-Ia serum, but not by anti-H-2 serum.