Rabbits were immunized by repeated intravenous injections of large amounts of chylomicrons plus VLDL isolated from human lipemic plasmas. The antisera were absorbed usccessively with lipoprotein free serum, HDL and LDL2. The absorbed antisera still precipitate chylomicrons and VLDL from sera of normal and hyperlipemic subjects (post-absorptive donors and fasting patients with type IV and type V hyperlipoproteinemia). By gel diffusion methods (immunoelectrophoresis and double diffusion in two dimensions), the antisera reveal a single precipitin line which stains better for lipid than for protein. This line is pronounced in VLDL-rich sera and absent in VLDL-free sera. The antisera react with chylomicrons plus VLDL delipidated by extraction with ethanol/diethyl ether; this shows that the antigenic site is an apoprotein; in contrast to apoprotein C, this apoprotein appears to be unique to the triglyceride-rich lipoproteins.