The mechanisms involved in sustaining the high levels of ornithine decarboxylase (ODC) activity in human cancers are not well defined. We examined the level of expression of ODC mRNA together with ODC activity in surgically excised human cancers, including esophagus, stomach, colon, and liver tumors, the objective being to determine whether the ODC mRNA level correlates with enhancement of ODC activity in these cancers. Among these tumors, the esophageal cancers had the highest ODC activity (120 +/- 43.9 pmol of CO2/h/mg of protein), compared with the stomach (37.6 +/- 13.7), colon (22.8 +/- 5.9), and liver (10.2 +/- 5.6) cancers. A remarkable increase in ODC mRNA was seen in all of the esophageal cancers. The ratio of ODC mRNA in the tumors, relative to the paired normal tissues, was 14.6 +/- 3.7. Some increase was noted in some of the stomach (2.9 +/- 0.9) and colon (2.1 +/- 0.9) cancers, but there was no increase in the liver tumors (0.9 +/- 0.2). A significant correlation was noted between ODC activity and mRNA expression in cancerous and noncancerous tissues of the esophagus, stomach, and colon, thereby suggesting that increased steady-state mRNA may be responsible for the high ODC activity in these tumors. Southern blot analysis of the DNA from the esophageal cancers revealed no amplification or significant rearrangement of the gene. Mechanisms sustaining high ODC mRNA levels in esophageal cancers may be an enhancement of the promoter activity of this gene or stabilization of the mRNA.