The use of a B-lymphoblastoid cell line (B-L-CL) as a stimulator cell in the mixed leukocyte reaction (MLR) was investigated in patients with immunodeficiency disorders. The kinetics of the MLR stimulated by B-L-CL are similar to those stimulated by normal allogeneic leukocytes, however, B-L-CL stimulate a greater quantitative response. Comparison of a LCL-stimulated and normal allogeneic lymphocyte-stimulated MLR in 32 patients and normal controls demonstrated that variation in the MLR was reduced when B-LCL were used as stimulator cells. The decrease in variability allowed for more sensitivity in the determination of abnormal responses; 9 of 32 patients had abnormal B-LCL-stimulated MLC responses, compared with 5 of 32 patients with abnormal responses to normal allogeneic leukocytes. Dose-response studies showed that vigorous responses could be obtained with low doses of B-LCL stimulator cells which served to better define deficient patient responses. Several patients demonstrated dissociation between the B-LCL-stimulated MLR and mitogen responses. The use of a B-LCL as a stimulator in the MLR is a valuable tool for the assessment of the immune status of patients with a variety of immunodeficiency disorders.