Sera from the elderly, but not young, inhibited markedly interleukin 2 (IL-2)-dependent proliferation of cloned T cells. Sera of aged humans contained high levels of tri-glyceride, cholesterol, very low density lipoproteins (VLDL) and low density lipoproteins (LDL). VLDL and LDL inhibited the proliferation in a dose-related manner. The inhibition correlated with levels of serum VLDL and LDL. These results suggest that lipoproteins may act as a regulator of IL-2-dependent proliferation and that disturbance of lipid and lipoprotein metabolism may be partially responsible for diminished immune responses in the elderly.