Studies on the level of serum type IV collagen (IV C) have usually been focused on the disease with diffuse hepatic fibrosis. To investigate whether serum level of IV C was predictive for the development of liver cancer as well as liver cirrhosis, serum IV C level was measured by a one-step sandwich enzyme immunoassay. The mean level of serum IV C was 73.3 +/- 31.3 ng/ml in 48 controls. The levels (ng/ml) of IV C were 396.4 +/- 254.9, 429.6 +/- 320.7, 420.6 +/- 322.8, and 362.9 +/- 247.4 respectively in 11 patients with chronic hepatitis, 11 with liver cirrhosis, 16 with hepatocellular carcinoma (HCC) with cirrhosis, 10 with HCC without cirrhosis, and 10 with metasatic liver cancer, which were significantly higher than that in controls (p < 0.05). Serum IV C levels were also evaluated using a cut-off value which was determined as the mean plus two standard deviations in the controls, 136 ng/ml. The elevations above the cut-off value were observed in 91, 100, 80, and 90% respectively of 11 patients with cirrhosis, 16 with HCC with cirrhosis, 10 with HCC without cirrhosis, and 10 with metastatic liver cancer, while only one (9%) of 11 chronic hepatitis patients and none (0%) of 48 controls had elevated levels. The levels of serum IV C were analysed with regard to age, sex, serum levels of albumin, globulin, transaminases, alpha-fetoprotein, and diameter of liver mass, a significant difference being observed only between the diameter of HCC and serum level of IV C (p < 0.01). These results indicate that the measurement of serum IV C is a useful for the determination of primary and metastatic liver cancer as well as liver cirrhosis.