Epstein-Barr virus (EBV)-induced immortalization of adult human B lymphocytes is suppressed by physiologic concentrations of human plasma lipoproteins. Several inhibitory mechanisms appear to be operative. First, low density lipoproteins (LDL) directly reduce the ability of EBV to transform human B cells. Second, LDL as well as intermediate and very low density lipoproteins modulate early inductive events rendering the B cell refractory to transforming signals from EBV. Third, LDL also selectively inhibit an EBV-inducible step that occurs within 24 h after transformation. Finally, very low density lipoproteins can abrogate the ongoing, cellular proliferation of EBV-transformed, established B cell lines. The plasma lipoproteins may therefore prevent the emergence of EBV-transformed malignant B cell clones in vivo. Conceivably, on this basis, environmental and genetic influences on plasma lipoprotein concentrations may affect the global distribution of Burkitt's lymphoma, a lymphoid malignancy putatively caused by EBV.