A case of Barrett's esophagus of the specialized columnar type is described in which mucosal ornithine decarboxylase levels were measured in endoscopic biopsies at two intervals over which severe dysplasia had developed. The Barrett's mucosa extended 5 cm above the gastroesophageal junction, was free of dysplasia, and had no detectable ornithine decarboxylase activity at initial evaluation. On follow-up endoscopy one year later, the Barrett's mucosa had become dysplastic with a markedly elevated ornithine decarboxylase activity of 1.56 units/mg protein. The patient underwent an esophagectomy because of persistent severe dysplasia and continues to do well postoperatively. Elevated ornithine decarboxylase activity has been described in other premalignant conditions, especially when dysplasia has been present. Further studies in Barrett's esophagus are warranted, since ODC activity might prove to be a useful biochemical marker for dysplasia and increased cancer risk.