Lipoproteins, chylomicrons (CM), very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) and acetyl modified LDL (AcLDL) can stimulate natural killer (NK) cells upon binding to specific receptors. Using flow cytometry and a specific monoclonal antibody against phosphotyrosine, we assessed the effect of lipoproteins on total intracellular expression of immunoreactive phosphotyrosine. Tyrosine phosphorylation increased when lipoproteins were added to purified NK cells, previously cultured overnight in RMPI-0.5% fatty acid free bovine serum albumin. The optimal effect occurred at 15 minutes for all the lipoproteins used. The concentrations of lipoprotein were 10 μg of protein/ml of CM, and 20 μg of protein/ml for the other lipoproteins. The effect of lipoproteins on phosphotyrosine positivity was as follows: LDL> VLDL >CM > HDL >AcLDL. Thus lipoproteins may activate NK cells through tyrosine phosphorylation and this signal transduction pathway seems to be enhanced when these cells are activated with LDL.