Cytotoxic activity of polymorphonuclear leukocytes (PMN) in the peripheral blood of patients with various diseases was demonstrated to K562 cells (natural cytotoxicity, NC) and the antibody-coated P815 cells (antibody-dependent cellular cytotoxicity, ADCC, using a 51Cr-release method. The NC values of normal PMN were lower than those of normal lymphocytes with mean values of 5.0% and 30%, respectively. The NC values of patients' PMN were also lower in malignancy, chronic hepatitis and connective tissue diseases. The ADCC values of normal PMN were moderately high with a mean value of 16.0%, which was almost a half of normal lymphocytes. Higher ADCC values of PMN were found in patients with chronic hepatitis, SLE and Behcet's disease, and in these cases the ADCC values of their lymphocytes were extremely low. The supernatants of PMN mix-cultured with unlabeled K562 or the antibody-coated P815 cells were fairly cytotoxic to both cells, though the similar supernatants of lymphocytes were cytotoxic only to K562 cells, but not to the antibody-coated P815 cells. -NC; ADCC; lymphocytes; PMN; SLE Polymorphonuclear leukocytes (PMN) in the peripheral blood have been recently found to possess cytotoxic effect on the target cells either with direct contact (Hafemann and Lucas 1979) or in combination with antibody (Hafemann and Lucase 1979;Gale and Zighelboim 1975;Zighelboim et al. 1976;Clark and Klebanoff 1977). The mechanism of the antibody-mediated cytotoxicity of PMN has been conveniently explained by the presence of IgG-Fc receptor on the PMN (Zighelboim et al. 1976), and the cytotoxicity of PMN has been assumed to be mediated by enzymes and active oxygens from PMN (Goldstein et al. 1975;Cheson et al. 1977;Segal et al. 1978).This paper reports the cytotoxicity of PMN of patients with various diseases tested to the 51Cr-K562 cells and the antibody-coated 51Cr-P815 cells in comparison with the cytotoxicity of lymphocytes.In order to analyze the mechanism of the PMN-mediated cytotoxicity, the supernatants of PMN obtained in mix-culture with the unlabeled target cells were