Repeated attempts with different assays and experimental conditions failed to detect significant peripheral blood lymphocyte reactivity in one-way mixed lymphocyte reactions to irradiated or mitomycin C-treated cells of the “leukemic” T lymphoid line RPMI 8402. In contrast, consistently high levels of peripheral blood lymphocyte reactivity were obtained with cells of six B lymphoid lines established from the same blood sample used to initiate this T lymphoid line. Although attempts to define the reason why these cultured T cells did not initiate a mixed lymphocyte reaction were not successful, evidence indicates that this inability may be an intrinsic characteri stic common to three other T lymphoid lines (MOLT-4, CCRF-CEM, and CCRF-HSB-2), also established from patients with relapsed acute lymphoblastic leukemia.