To evaluate the role of plasma des-gamma-carboxyprothrombin in the early diagnosis of hepatocellular carcinoma, we simultaneously studied both des-gamma-carboxyprothrombin activities by staphylocoagulase method and des-gamma-carboxyprothrombin antigen levels by enzyme immunoassay in 39 patients with early stage hepatocellular carcinoma (tumor size less than 3 cm in 21 patients, 3 to 5 cm in 18 patients); 68 patients had large hepatocellular carcinoma and 54 patients had chronic hepatitis or cirrhosis. Des-gamma-carboxyprothrombin levels by staphylocoagulase method (X) and enzyme immunoassay method (Y) on the same plasma specimens of hepatocellular carcinoma patients showed a linear correlation (Y = 0.15X - 10.5, r = 0.533, n = 67, p less than 0.001). Elevated des-gamma-carboxyprothrombin activities were present in 10 of 21 patients (47.6%) with hepatocellular carcinoma less than 3 cm, 66.7% of 18 with hepatocellular carcinoma 3 to 5 cm, 67.6% of 68 with hepatocellular carcinomas greater than 5 cm and 27.8% of 54 with chronic hepatitis or cirrhosis. The plasma des-gamma-carboxyprothrombin levels did not correlate with the tumor size or serum alpha-fetoprotein levels. Plasma des-gamma-carboxyprothrombin and serum alpha-fetoprotein measurements were comparable in the diagnosis of hepatocellular carcinoma because 22 (56.4%) and 21 (53.8%) of 39 patients with hepatocellular carcinoma less than 5 cm had increased des-gamma-carboxyprothrombin and alpha-fetoprotein levels, respectively. Up to 77% had an abnormal elevation in either marker.(ABSTRACT TRUNCATED AT 250 WORDS)