A liver-specific lipoprotein (LSP) which is present in 105,000 g supernatants of human liver has previously been shown to produce a lesion resembling chronic active hepatitis in rabbits immunized with human liver fractions containing this lipoprotein. In addition, it has been implicated as the principal target antigen involved in the liver cell cytotoxicity exhibited in vitro by lymphocytes from patients with chronic active hepatitis. The organ-specificity and species cross-reactivity of LSP is confirmed. Although very labile, is has been prepared in a stable form by gel filtration of Sepharose 6B in a Tris buffer containing 1 mm disodium EDTA. LSP is also stable in a borate buffer containing EDTA but is unstable in a number of other buffer systems tested. When prepared by this method it contains approximately 2% albumin as the only detectable contaminant. Gel filtration studies on the apoprotein of LSP revealed that it has an apparent mol. wt of between 4 X 10(6) and 20 X 10(6). SDA-polyacrylamide gel electrophoresis indicated that the lipoprotein may be composed of up to thirteen sub-units of different molecular sizes.