Serum levels of CA 125 and markers reputed as specific for cancers in relevant locations (squamous cell carcinoma, SCC, carcinoembryonic antigen, CEA, CA 19.9, alpha-fetoprotein, AFP) were determined in 107 patients with gastrointestinal (GI) carcinomas. The aim of this study was to assess their individual and combined sensitivities, and the power of CA 125 in excluding primary ovarian epithelial cancer from GI primary. Serum CA 125 levels (in U/ml) ranged from nondetectable to 400 in patients with esophageal, to 570 in those with gastric, and to 300 in patients with colorectal carcinoma. The levels for liver secondaries, pancreatic, and hepatocellular carcinoma were 480, 2,720 and 1,100 U/ml, respectively. Serum SCC antigen was elevated in all patients with esophageal cancer, CEA or CA 19.9 in 52% of patients with gastric cancer and in 63% with liver secondaries, and CEA in 95% of patients with colorectal cancer; whereas serum CA 125 above 65 U/ml was found in 25% of this subgroup, but only in those with already an elevated concentration of specific marker(s). Serum CEA or CA 19.9 was elevated in 71%, CA 125 in 59% of patients with pancreatic cancer; the latter mostly in those with already elevated CEA or CA 19.9. Serum AFP was elevated in 84% and CA 125 in 40% of patients with hepatoma; the latter mostly in those with already an elevated AFP. CA 125 values exceeding 1,000 U/ml were found in 1 patient with pancreatic cancer (2,720 U/ml) and in 2 with hepatoma (1,050 and 1,100 U/ml). These findings illustrate the nonspecificity of the CA 125 antigen, its small if any advantage compared to the specific markers, and they diminish its role as a marker for primary ovarian cancer from GI primary unless it exceeds 2,800 U/ml.