The authors studied 16 consecutive patients with chronic neutropenia of uncertain etiology in whom bone marrow biopsies were performed. Using monoclonal antibodies, they measured the levels of the two major subclasses of T lymphocytes, cells with the T-suppressor/cytotoxic cell phenotype (Ts), and cells with the T helper/inducer cell phenotype (Th) in the blood of eight of these patients. Five patients had Ts lymphocytosis or increased proportions of Ts cells and Th lymphocytopenia. All five patients had greatly increased proportions of large lymphocytes with prominent cytoplasmic azurophilic granules. Since cells with similar morphology from normal individuals have been shown to express cytotoxic activities, the authors measured the cytotoxic function of cells from three of the patients with Ts lymphocytosis. All three possessed antibody-dependent cell-mediated cytotoxicity (ADCC) but not natural killer (NK) cell activity. Many patients had evidence of autoimmune disorders, conditions in which Ts cells usually are decreased. None had hypogammaglobulinemia, a disorder that has been associated with increased Ts activity. The high incidence of an imbalance in T lymphocyte subpopulations in patients with neutropenia suggests that disturbed immunoregulation involving T cells may play an important role in the pathogenesis of this disorder.