Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.