In order to study the primary structure of rabbit apolipoprotein (apo) E and the regulation of levels of liver apo E mRNA by dietary cholesterol, we have cloned and sequenced a full length rabbit apo E cDNA. DNA sequence analyses suggests that rabbit apo E is synthesized with an additional 18 amino acids as the prepeptide. The mature rabbit apo E contains 293 amino acids with a calculated molecular weight of 33,528. It has a 76% amino acid sequence homology with human apo E. Northern blot analyses showed that rabbit apo E mRNA is about 1200 nucleotides in length. Using mRNA dot blot analyses, we found that dietary cholesterol has no effect on the level of apo E mRNA in rabbit liver. We conclude that the elevated levels of plasma apo E in rabbits fed a cholesterol-rich diet is not a result of an increase of levels of apo E mRNA in the liver.