We evaluated the proapolipoprotein A-I (proapo A-I)-converting activity to clarify the pathogenesis of the high proapo A-I/apo A-I ratio in the high-density lipoprotein (HDL) from patients with acute hepatitis and liver cirrhosis. The serum proapo A-I-converting activities were measured using 3H-labeled proapo A-I. 3H-labeled proapo A-I was purified from the media of cultured Hep G2 cells by immunoaffinity chromatography. The serum proapo A-I-converting activities were found to be significantly reduced in the patient with liver cirrhosis (140 +/- 53 dpm/ml per h) or acute hepatitis (140 +/- 48 dpm/ml per h) compared to normal subjects (315 +/- 32 dpm/ml per h). Serum proapo A-I-converting activity has a positive correlation with liver function tests such as serum albumin, choline esterase activity, ICG clearance and inverse correlation with proapo A-I/apo A-I ratio in HDL. These results suggest that the high proapo A-I/apo A-I ratio is due to the decreased proapo A-I-converting activity, and that the liver plays a significant role in the conversion of proapo A-I to apo A-I.