We developed a quantitative method of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction. With this method, 36 patients with type C chronic liver disease were analyzed for the copy number of circulating hepatitis C virus in 50 microliters of serum. The amounts of hepatitis C virus RNA ranged from 10(1) to 10(7) copies in the 36 patients. The average amount of hepatitis C virus RNA was 10(3.3 +/- 2.2) copies in 12 patients with chronic persistent hepatitis, 10(5.7 +/- 1.6) copies in 12 patients with chronic active hepatitis and 10(6.0 +/- 1.6) copies in 12 patients with cirrhosis (including 4 patients with hepatocellular carcinoma). The amount of hepatitis C virus RNA in serum was significantly less in patients with chronic persistent hepatitis than in patients with chronic active hepatitis or cirrhosis (p < 0.01), and it tended to increase according to the progression of histopathological changes of the liver. Furthermore, it was revealed that the amount of hepatitis C virus RNA became exponentially larger as the term from infection became longer. Quantification of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction may have many applications for the study of clinical features of hepatitis C virus infection.