Phenotypic and functional aspects of cellular cytotoxicity were investigated in patients after splenectomy. While assays testing for natural killer cell (NK) activity and antibody-dependent cellular cytotoxicity showed a significantly reduced (p less than 0.005 and p less than 0.025, respectively) activity of the relevant cell populations, lectin-dependent cellular cytotoxicity was either normal or, in one dilution of phytohemagglutinin, even significantly increased (p less than 0.025), as compared to healthy control persons. In a search for a possible explanation for this phenomenon, it was found that the total lymphocyte count was significantly increased (p less than 0.01) in patients after splenectomy, when compared with healthy control individuals. However, neither the absolute cell count nor the percentage of Leu7+ lymphocytes showed significant differences between splenectomized patients and controls. In contrast, the percentages of (Leu7+Leu2)+, OKT11+, OKT4+ and Leu2a+ lymphocytes were significantly decreased (p less than 0.0025, p less than 0.01 and p less than 0.005, respectively) in splenectomized patients with not only the percentage, but also the absolute number of DR+ lymphocytes being significantly increased (p less than 0.005 and p less than 0.05, respectively). We thus conclude that in patients after splenectomy NK activity is decreased which may possibly be due to the lack of a NK subset. In contrast, the overall percentages of T cells (OKT11+), T helper/inducer (OKT4+) and T suppressor cells (Leu2a+) were significantly decreased in patients after splenectomy, although this defect could be compensated by a significant increase in the absolute lymphocyte number.