Normal lymphocytes respond to the presence of allogeneic lymphocytes in culture with a high uptake of 3H-thymidine. We present a study of the interaction of chronic lymphatic leukemia (CLL) lymphocytes with normal allogeneic lymphocytes using the one-way mixed lymphocyte culture technique of Bach. The lymphocytes of 11 patients with CLL were tested separately against those of four normal subjects. In all 11 patients an impaired responsiveness was found. The mean response of CLL lymphocytes to those of the control panel was 19,805 cpm, whereas the mean response of panel lymphocytes to CLL lymphocytes was 90,319 cpm (p < 0.001). There was no significant difference between the mean response of panel lymphocytes to CLL lymphocytes and to those of other panel members (81,630 cpm). Therefore, CLL lymphocytes display an impaired responsiveness to allogeneic lymphocytes, while their capacity to stimulate is intact. These results are in accord with their previously demonstrated impaired reactivity to phytohemagglutinin, a less specific mitogenic stimulus, and serve as further evidence of defective cellular immune response in CLL.