Alpha-fetoprotein (AFP) was determined by a new radioimmunoassay in the sera of patients with different liver diseases. Compared to a normal group (n = 140, AFP levels below 15 ng/ml), most elevated AFP concentrations were found in 18 patients with primary liver cancer (PLC), 7 of whom showed Ouchterlony-positive levels (above 10,000 ng/ml). In 3 cases with liver cirrhosis, PLC was first suggested by high AFP levels between 1000 and 3600 ng/ml and later confirmed by histology. On the other hand, only 6 from 15 patients with other primary tumors and liver metastasis had AFP concentrations between 20 and 111 ng/ml. In 90% of 102 patients with liver cirrhosis AFP levels below 20 ng/ml were determined, while 13 cases showed elevated values up to 134 ng/ml. A transitory AFP increase between 20 and 238 ng/ml was seen in 32% of 63 cases in the early stage of acute hepatitis but 65% of 31 these cases in follow-up studies. 3 of 7 cases of chronic hepatitis gave similar results. The maximal AFP levels developed following the maximal transaminase activities by 5-18 days and coincided with a decrease of cholinesterase activity. The radioimmunological determination of AFP is recommended for earlier detection of the development of PLC in liver cirrhosis patients.