Soluble HLA Class I antigens in sera (serum-HLA Class I, s-HLA Class I) of patients with chronic hepatitis (CH) were measured with an enzyme-linked double determinant immunoassay (E-DDIA). The mean titers of s-HLA Class I antigens of patients with CPH (mean +/- standard deviation, 2.22 +/- 1.60), CAH2A (2.24 +/- 1.65) or CAH2B (2.73 +/- 1.46) were significantly higher than that of normal subjects (0.36 +/- 0.27) (P less than 0.01). The titer of s-HLA Class I correlated significantly with the level of serum glutamic pyruvic transaminase (s-GPT) (r = 0.73), and weakly with serum level of beta 2-microglobulin (r = 0.43). In patients with chronic hepatitis type B (CH-B) treated with human lymphoblastoid interferon alpha (IFN-alpha), the titer of s-HLA Class I antigens increased. The increased level of s-HLA Class I antigens in the clinical course of chronic hepatitis may be caused by their release from necrotizing hepatocytes which have acquired the expression of HLA Class I antigens on the cell-surface membrane during viral infection.