The effects of human high density lipoproteins, low density lipoproteins and very low density lipoproteins on spontaneous plaque forming cell (PFC) generation have been evaluated in healthy donors. Additionally, natural killer (NK) cytotoxicity using either 51Cr release assay or agarose single cell system has been studied under identical experimental conditions. A significant inhibition of spontaneous PFC capacity was observed. Furthermore, lipoprotein (LP) pre-treatment led to a reduced frequency of cells mediating NK cytotoxic activity as shown by the decreased binding capacity, even if the killing function was per se not affected. Taken together, these results suggest an inhibitory role for human LP on certain immune functions, likely related to the imbalance of lymphocyte metabolic pathway.