Leukemia cells from 13 of 27 patients stimulated lymphocytes of their HLA-identical siblings in mixed leukocyte cultures (MLC). Stimulation correlated with high background uptake of tritiated thymidine and high percentages of cells that stained with fluorescein-conjugated polyvalent goat antiserum against human immunoglobulin. Results were similar to those reported with fractionated autologous lymphocyte subpopulations in normal individuals. Investigation of leukemia-specific stimulation in MLC is therefore problematic.