A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell-associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21-31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.