Natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes from untreated non-Hodgkin's lymphoma patients were found to be depressed, when tested against the human erythroblastoid cell-line K562. The percentage of active killer (AK) cells and that of target binding cells (TBC) of the patients were also inhibited. Treatment of the patients lymphocytes with interferon (IFN) caused an augmentation in their NK activity which was comparable with that seen in the controls. Lymphocytes from some of the patients and controls were cocultured with K562 cells for production of natural killer cytotoxic factors (NKCF). The NKCF released by the patients lymphocytes showed a reduced lytic activity against K562 target cells. The depression in all the activities reported here showed a correlation with the clinical status of the patients except in the case of ADCC. These results indicate that further characterization of the properties of NKCF will contribute the understanding of the mechanism of NK cytotoxicity.