The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from patients with malignant lymphoma was examined. In 54 untreated patients, the mean NK activity did not differ significantly from that in healthy controls. However, 17 (31%) of 54 patients showed low NK activity. NK activity did not correlate with the stage, histologic type or patient age. Significant reduction of NK activity was observed during combination chemo-therapy. The mean NK activity in complete respondors (CRs) did not differ significantly from that in healthy controls. However, 5 (14%) of 37 patients who were disease-free for more than 3 years showed low NK activity. Low NK activity was frequently observed in long-term CRs with non-Hodgkin's lymphoma compared with negative PPD skin test, negative PHA skin test, low CD4/CD8 ratio and decreased response of PBMC to PHA and/or Con A. These results indicate that patients with malignant lymphoma have decreased immunity even while in long-term continuous remission and that measuring NK activity is useful for evaluating their immunologic status.