Natural killer (NK) cell activity was measured in the peripheral blood mononuclear cells (PBMC) from malnourished (MN) and well-nourished (WN) cancer patients and in healthy controls. A marked depression of NK activity was observed in MN cancer patients with moderate protein-calorie malnutrition (PCM), but not in WN cancer patients nor in the healthy controls. The depression of NK activity did not correlate with the localisation of the tumour, patient's age or body weight reduction. The defective NK activity of PBMC from MN cancer patients was restored to normal by rIL-2, but not by alfa-rIFN. Parenteral nutrition of MN patients with the proper amount of proteins and calories quickly corrected the depressed NK activity, indicating a central role of malnutrition in the genesis of their immune disfunction. PBMC from MN cancer patients produced lower amounts of IL-2, as compared with healthy controls, when stimulated in vitro; the most frequently affected were the responses to recall antigens such as influenza virus vaccine (FLU), while those to allogeneic PBMC (ALLO) and phytohaemagglutinin (PHA) were less affected. However, for each patient the ability to produce IL-2 in vitro did not correlate with NK activity, thus showing how the impairment of NK activity is not subsequent to a decreased production of endogenous IL-2. In summary, it can be concluded that malnutrition, rather than malignancy, plays a major role in the immune dysfunction of cancer patients.