Fetal liver produces an alpha-1 globulin called “alpha fetoprotein” (AFP), which becomes the dominant fetal serum protein in the first trimester, reaching a peak at 12 weeks, then declining to 1% of the peak at birth. By age 1 year, a much greater decrease has occurred. Primary liver cell carcinomas (hepatomas) were found to produce a similar protein; therefore, a test for hepatoma could be devised using antibodies against AFP antigen. Original techniques, such as immunodiffusion, were relatively insensitive and could not detect normal quantities of AFP in adult serum. Extensive studies using immunodiffusion in several countries revealed that 30%-40% of European hepatoma patients who were white had positive test results, whereas the rate among Chinese and African Americans with hepatoma was 60%-75%. Men seemed to have a higher positive rate than women. Besides hepatoma, embryonal cell carcinoma and teratomas of the testes had an appreciable positivity rate. Reports of false positive results with other conditions included several cases of gastric carcinoma with liver metastases and a few cases of pregnancy in the second trimester. Subsequently, when much more sensitive radioimmunoassay techniques were devised, small quantities of AFP were detected in normal adult individuals. RIA and EIA have increased the abnormality rate in hepatoma somewhat, especially in European patients, whereas elevations accompanying other conditions are also more frequent. For example, according to one report, AFP levels were increased in approximately 75% of hepatoma cases, 75% of embryonal carcinomas or teratomas of the testes, 20% of pancreatic or gastric carcinomas, and 5% of colon and lung carcinomas. Others have found AFP elevations by immunoassay methods in 90% or more of hepatomas (literature range, 69%-100%) and in 0%-5% of various nonneoplastic liver diseases. The most frequent nonneoplastic elevations occurred in conditions associated with active necrosis of liver cells, such as hepatitis and active alcoholic cirrhosis. An AFP level of 500 ng/ml was suggested by several investigators as a cutoff point in differentiating hepatoma from nonneoplastic liver disease. Almost all of the nonneoplastic disease (except some cases of hepatitis virus hepatitis) were less than 500 ng/ml, whereas 50% or more patients with hepatoma had values higher than this.