Severe liver dysfunction is often associated with alterations of plasma lipids and lipoproteins. In this study the high-density lipoprotein (HDL) class has been further investigated. HDL from patients with acute, cholestatic hepatitis (n = 10) was isolated and compared with that of normals. Lipid and protein analyses were performed during the acute stage of the disease, with consequent follow-up studies. It was found that (1) only apo A-I was decreased by 50% in the isolated HDL fractions, whereas apo A-II remained unchanged; apo A-I in total plasma was normal; (2) immunoelectrophoresis of hepatitis HDL against monospecific anti-A-II revealed one precipitin line but two or more bands against anti-A-I; (3) concomitant with an increase of phospholipids and a decrease of triglycerides and the total cholesterol fraction, hepatitis HDL contained 10--12 times more bile acid than normal HDL. Chenodeoxycholic acid was the predominant bile acid. These alterations were fully reversible when patients recovered. These parameters seem to be sensitive markers for the degree of disturbance and restoration of liver function. The structural-functional implications of the observed compositional changes of HDL during cholestasis are discussed.