Lipoprotein lipase (LPL) is the key enzyme in the metabolism of triglyceride-rich lipoproteins. The patterns of LPL mRNA expression and secretion of the enzyme have not yet been established in natural killer (NK) cells. We show in the present communication that CD3- CD16+ cells (NK cells) transcribe LPL mRNA, express LPL on the surface and secrete the enzyme. In contrast, there is no LPL expression on the surface of highly purified B and T lymphocytes. Stimulation of NK cells with interleukin-2 (IL-2) reduced the expression of LPL on their surface and augmented the secretion of LPL by the cells. The addition of anti-LPL antibodies to NK cells in culture led to a complete abrogation of cytotoxicity of NK cells against the K562 tumour cell line. Furthermore, IL-2 stimulation of effector cells reversed the anti-LPL antibody-induced inhibition of cytotoxic activity. Overall, these findings suggest that LPL plays a key role in the cytotoxic activity of NK cells.