Apolipoprotein E (apoE), but not apoAI or apoCIII, suppresses mitogen-activated T lymphocyte proliferation, independent of the type of activation signal. Both CD4 and CD8 T cells are inhibited. ApoE inhibits T cell proliferation, in part, by reducing the production of bioactive interleukin 2 (IL2). IL2 activity is reduced by approximately 50-65% in cultures of mitogen-stimulated T cells when apoE is present. ApoE does not significantly alter levels of IL2 mRNA or the mass of secreted IL2 protein, quantitated by enzyme immunoassay. Reduced IL2 activity was not a consequence of induction of IL2 inhibitors in response to apoE or effects of apoE on the bioassay. These results suggest that apoE antagonizes post-translational events in mitogen-activated T lymphocytes that are required for the secretion of a bioactive IL2 protein.