T-cell regulation of pokeweed mitogen (PWM)-induced polyclonal immunoglobulin (Ig) production was studied in mice. Under optimal stimulating conditions, about 1000 Ig-producing cells were generated per 3 x 10(5) spleen cells and macrophages were required to generate Ig-producing cells from B lymphocytes. The response of splenic B cells to PWM was partially dependent upon helper T cells, whereas the response to lymph node B cells was completely dependent upon T cells. Helper activity was attributed not only to Lyt 1+ 2- but also to Lyt 1+ 2+ T cells. Co-operation between T and B cells, in this system, was not restricted by H-2 barrier.