To evaluate the diagnostic value of alpha-1-antitrypsin (alpha-AT) as a tumor marker for hepatocellular carcinoma (HCC), we studied the serum levels of alpha-AT by rocket immunoelectrophoresis and alpha-fetoprotein (alpha-FP) by radioimmunoassay in 46 proven HCC patients, 43 cirrhosis patients and 200 healthy blood donors. The mean alpha-AT level of the 46 patients with HCC (4.8 +/- 2.7 mg/ml) was significantly higher than that of 200 healthy control subjects (1.7 +/- 0.7 mg/ml) (P < 0.0001). The sensitivity of alpha-AT in 24 patients with high level of alpha-FP (> 400 ng/ml) and 22 patients with low level of alpha-FP (< 400 ng/ml) were 96% and 64%, respectively. There was no substantial correlation between alpha-FP and alpha-AT in the two groups (alpha-FP > 400 ng/ml, alpha-FP < 400 ng/ml) (r = 0.078, 0.064). The sensitivity for HCC using alpha-FP level alone (> 400 ng/ml) was only 52%, and the sensitivity using alpha-AT level alone (> 3.2 mg/ml) was 76% of the 46 patients. Combining both tests, sensitivity was improved only to 80%.