Serum alpha-fetoprotein levels were measured by a sensitive double-antibody radioimmunoassay in 580 patients with a variety of malignant and nonmalignant gastrointestinal diseases to determine the incidence of levels elevated above 40 ng/ml. Over 200 normal control subjects have all had levels below 40 ng/ml. Fifteen % of 95 patients with gastric carcinoma, 3 percent of 191 patients with colorectal carcinoma, 24 percent of 45 patients with pancreatic carcinoma, 25 percent of 8 patients with biliary tract carcinoma, and 70 percent of 73 patients with hepatocellular carcinoma had elevated serum alpha-fetoprotein. None of 14 patients with esophageal or small bowel carcinoma had elevated levels. In contrast, 1 percent of 154 patients with nonmalignant, nonhepatic gastrointestinal disease had elevations of serum alpha-fetoprotein. Alpha-Fetoprotein appears to be a potential marker for tumor activity in some patients with certain gastrointestinal cancers.