The Lewis (Le) phenotype of both erythrocytes and sera and serum CA19-9 levels were studied in 49 patients with pancreatic carcinoma, in 37 with gastric cancer, in 22 with colorectal cancer, in 21 with bile duct carcinoma, and in 19 with hepatocellular carcinoma. The Le phenotype was determined in sera with the use of the dot-immunobinding assay and on erythrocytes. The localizations of the Le antigen and CA19-9 were studied in pancreatic tissues from 22 patients with pancreatic carcinoma. The prevalence of Le(a-,b-) on erythrocytes was significantly higher in patients with pancreatic carcinoma than in normal controls. Nineteen of 21 patients with pancreatic carcinoma, whose Le phenotype on erythrocytes was Le(a-,b-), had Le antigen in tissues and sera, and they had a raised serum CA19-9 level. The remaining 2 patients were of the Le(a-,b-) phenotype for both erythrocytes and sera, and their serum CA19-9 levels were below 6 U/ml. Neither Le antigen nor CA19-9 could be localized in tissues of these 2 patients. Two patients with gastric cancer, 6 with colorectal cancer, and 6 with bile duct carcinoma had Le antigen in sera in spite of having Le(a-,b-) on erythrocytes. These results indicate that the Le phenotype on erythrocytes can undergo a change not infrequently in patients with pancreatic carcinoma as well as in patients with other gastrointestinal cancers, but patients with the Le(a-,b-) phenotype in sera cannot synthesize CA19-19.