In our effort to study proteins that are involved in high density lipoprotein metabolism, we have identified apolipoprotein F and isolated a full length cDNA clone. Apolipoprotein F, with an apparent molecular mass of 29 kilodaltons, was purified from human high density lipoproteins using a modified two dimensional electrophoresis procedure. The cDNA, with a size of 1735 base pairs, was cloned from a Hep G2 cDNA library. The cDNA encodes apolipoprotein F, which is composed of 162 amino acids, and predicts that apolipoprotein F is a proteolytic product of a larger protein. Northern blot analysis indicates that apolipoprotein F mRNA is detected only in liver for the tissues examined. The gene was mapped to human chromosome number 12 using a human/rodent somatic cell hybrid mapping panel.