Natural killer (NK) cell numbers and T lymphocyte subpopulations in peripheral blood were evaluated in six patients with aplastic anemia (AA). The immunophenotyping results were correlated to in vitro tests of NK cell cytotoxicity against K562 cells and of immunoglobulin (Ig) production after pokeweed mitogen (PWM) stimulation. A significant decrease was found both in the percentage of Leu 11 positive cells and in NK cell activity as compared to age- and sex-matched healthy controls. The decrease in NK cell activity could not be entirely compensated by an increase in effector/target cell ratios, thus suggesting not only a quantitative but also a functional defect in NK cells of the AA patients. Three of four AA patients tested showed no major increase of Ig production after PWM stimulation. All these three patients also had fewer "functional T helper" cells (Leu3+/Leu8-) and increased numbers of T suppressor/cytotoxic cells (Leu2+) when compared to controls. No significant differences in numbers of B lymphocytes (B1+) could be found. Our findings suggest a possible linkage between quantitative and qualitative abnormalities in lymphocyte subsets in aplastic anemia. However, no evidence was found to support the hypothesis of increased NK cell activation behind the hemopoietic depression in this disease.