Our objective was to investigate the effect of interleukin-2 (IL-2) on the cytotoxic activity of natural killer (NK) cells in patients with chronic heart failure (CHF). Natural killer cells were isolated from 48 patients with CHF and 30 healthy subjects. The cytotoxic activities of the NK cells were assessed with the thiazolyl blue tetrazolium bromide (MTT) approach. Interleukin-2 (20 ng/ml) was added to the cell culture to stimulate the cytotoxicity of the NK cells. The cell number in the New York Heart Association (NYHA) class II, III, and IV was 27.9 ± 2.5, 21.2 ± 2.7, and 16.8 ± 2.6 cells/μl, respectively, which was significantly lower than in the control group (31.2 ± 3.6 cells/μl, all P < 0.01). The cytotoxic activities in NYHA II, III, and IV groups were 28.6% ± 3.2%, 16.0% ± 2.2%, and 12.1% ± 2.9%, respectively, which was lower than in the control group (41.0% ± 4.0%, all P < 0.01). Univariate analysis showed a close correlation between the NK cell cytotoxicity and the left ventricular ejection fraction (r = 0.949, P < 0.001). After in vitro treatment with IL-2, there was a significant increase in the cytotoxic activity of the NK cells in the control and the three heart failure groups (all P < 0.01). There is a significant reduction in the number and the cytotoxic activity of circulating NK cells in patients with CHF. The degree of NK cell deficiency is closely related to the severity of left ventricular dysfunction. In vitro treatment with IL-2 improves the cytotoxic activity of NK cell from the CHF patients.